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Minimally Invasive Percutaneous Treatment of Small Renal Tumors with Irreversible Electroporation: A Single-Center Experience
CLINICAL STUDY
Minimally Invasive Percutaneous Treatment of Small Renal Tumors with Irreversible Electroporation: A Single-Center Experience Clayton K. Trimmer, DO, Ankaj Khosla, MD, Monica Morgan, MD, Summer L. Stephenson, PA-C, Asim Ozayar, MD, and Jeffrey A. Cadeddu, MD
ABSTRACT Purpose: To evaluate whether irreversible electroporation (IRE) can be used as an ablation technique for small renal tumors (T1a cancers or small benign tumors) and to describe features after ablation on computed tomography (CT) or magnetic resonance (MR) imaging. Materials and Methods: In this retrospective study, 20 patients (mean age, 65 y ⫾ 12.8 y) underwent CT-guided IRE of T1a renal carcinoma (n ¼ 13) or small benign or indeterminate renal masses o 4 cm in size (n ¼ 7). Mean tumor size was 2.2 cm ⫾ 0.7. The ablation area was verified with contrast-enhanced imaging performed immediately after the procedure to determine technical success. Imaging was performed 6 weeks (20 of 20 patients), 6 months (15 of 20), and 12 months (6 of 20) after ablation. Medical records and CT/MR imaging features of all patients were reviewed for recurrence, symptoms, and complications after treatment. Results: Technical success was achieved in all patients (100%); there were no major procedure-related complications. Minor complications occurred in 7 patients, including self-limiting perinephric hematomas, pain difficult to control, and urinary retention. Mean procedure time was 2.0 hours ⫾ 0.7. At 6 weeks, 2 patients required salvage therapy because of incomplete ablation. At 6 months, all 15 patients with imaging studies available had no evidence of recurrence. At 1 year, 1 patient (1 of 6) was noted to have experienced recurrence. CT/MR imaging after IRE ablation demonstrated an area of nonenhancement in the treatment zone that involuted over 6 months. Conclusions: Renal IRE appears to be a safe treatment for small renal tumors. Tumors treated with IRE demonstrated nonenhancement in the treatment zone with involution on follow-up CT/MR imaging.
ABBREVIATIONS IRE = irreversible electroporation, RCC = renal cell carcinoma
Renal cell carcinoma (RCC) is one of the most lethal cancers in the United States, with approximately 63,000 new cases and 13,000 deaths annually (1). Several minimally invasive techniques, such as radiofrequency (RF) ablation, cryoablation, microwave ablation, and other
From the Departments of Radiology (C.K.T., A.K., S.L.S.) and Urology (M.M., A.O., J.A.C.), University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, TX 75390. Received March 25, 2015; final revision received June 19, 2015; accepted June 20, 2015. Address correspondence to C.K.T.; E-mail: [email protected] None of the authors have identified a conflict of interest. & SIR, 2015 J Vasc Interv Radiol 2015; XX:]]]–]]] http://dx.doi.org/10.1016/j.jvir.2015.06.028
thermal ablation techniques, have been developed and implemented to treat small renal tumors (T1a renal malignancies and small benign renal tumors o 4 cm in size). Numerous studies have shown the efficacy of these techniques as equivalent to partial nephrectomy (2–7). However, thermal ablation techniques have limitations. For example, thermal ablation can damage normal, non– tumor-containing tissues surrounding the target lesion (5); of particular concern are possible injuries to critical structures such as arteries, veins, small intestine, colon, ureter, or the renal collecting system (8). Meta-analyses have shown that the most common complications from RF ablation, cryoablation, and microwave ablation are paresthesias at the probe site, vascular injury, urothelial injury (usually self-contained urinoma), and bowel injury, although together they total o 5% (9–11). Also, all
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thermal ablation technologies are less effective in treating lesions near larger blood vessels secondary to the welldocumented heat sink effect (8,11,12). Irreversible electroporation (IRE) is a newer ablation method that can be used to treat small renal masses tumors o 4 cm). Because IRE employs a nonthermal ablation, IRE could permit the treatment of tumors in close proximity to critical structures, while preserving normal renal parenchyma, with decreased complications. Clinically, IRE has been reported to be effective in the treatment of pancreatic, lung, hepatic, renal, and adrenal lesions (13–18). In terms of renal application, two studies have shown that IRE is effective and limits damage to the treatment area of the ablated lesion within porcine kidneys (12,19). The purpose of this study was to determine the clinical efficacy and safety of in situ renal tumor ablation by IRE and to describe imaging features after ablation.
MATERIALS AND METHODS All patients were counseled by their treating physician regarding management options for small renal masses, including surgery, ablation, and active surveillance, and provided written and verbal informed consent for the IRE procedure. The patients were part of an institutional review board–approved retrospective institutional renal mass database. Records of all patients who underwent IRE for treatment of small renal masses at our institution were included in this retrospective study. The selection of ablation modality was determined by the provider based on size and location. Tumors particularly close to back and paraspinal muscles were selected for IRE with the intent to reduce pain after the procedure, which often occurs with thermal ablation. Patients with nodal or distant metastases and patients with multiple tumors ipsilaterally were excluded from the study.
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Table 1 . Patient and Tumor Characteristics in Technically Successful IRE Characteristic Average age (y) Average tumor size (cm)
Value 65 ⫾ 12.8 2.2 ⫾ 0.7
Comorbidities (no. patients) Coronary artery disease Hypertension
4 10
Diabetes
7
Chronic obstructive pulmonary disease Sleep apnea
5 1
von Hippel-Lindau disease
1
Other cancer diagnosis Average operating room time (h)
3 2.0 ⫾ 0.7
No. probes
3.7 ⫾ 0.7
Histology (no. patients) Clear cell
10
Papillary
3
Oncocytoma Not available
2 5
Location (no. patients) Upper pole Interpolar Lower pole
4 10 4
Creatinine before intervention (mg/dL) Creatinine 6 wk after intervention (mg/dL)
0.99 ⫾ 0.4 0.95 ⫾ 0.2
GFR before procedure (mL/min/1.73 m2)*
73.4 ⫾ 22.2
GFR after procedure (mL/min/1.73 m2)*
73.7 ⫾ 22.8
Note–Values are given as mean ⫾ SD or number. GFR ¼ glomerular filtration rate; IRE ¼ irreversible electroporation. *Our laboratory does not specify the exact GFR when values are Z 60 mL/min/1.73 m2. The average GFR was 4 60 mL/min/ 1.73 m2 in all patients, per our laboratory, before and after the procedure. We recalculated the GFR using the Modification in Diet in Renal Disease equation to obtain an actual GFR when not stated by our laboratory (20).
Imaging and Pathologic Diagnosis Patients The study comprised 20 patients (12 women and 8 men) with a mean age of 65 years ⫾ 12.8. In 16 patients, tumors were incidentally discovered on abdominal computed tomography (CT) or magnetic resonance (MR) imaging scans. Two patients had prior partial nephrectomies and were found to have new tumors on follow-up scans. One patient with von Hippel-Lindau disease had a tumor detected on screening CT. The final patient had an immunoglobulin G deficiency, and the tumor was detected as part of routine screening CT. At the time of diagnosis, 10 of the patients had a history of hypertension. Three patients presented with a diagnosis of an additional malignancy (prostate, bladder, and colon). The remaining comorbidities are listed in the Table. All of the tumor locations were peripheral (clear of any critical structures or vessels), which allowed us to assess the possibility of IRE more safely in this early experience.
All patients underwent initial imaging, either contrastenhanced MR imaging or CT, using established institutional renal mass protocols to confirm a renal tumor. Most patients (15 of 20; 75%) had biopsy confirmation of the renal tumor before or at the time of the procedure. The average tumor size was 2.2 cm ⫾ 0.7. Tumor size was determined based on the largest diameter on CT or MR imaging performed before the procedure. A needle biopsy diagnosis was made in 15 of 20 (75%) patients; 10 were clear cell–type cancers, two were oncocytomas (detected on biopsy at the time of ablation), and three were papillary-type cancers. Two patients had bilateral renal tumors. In one case, IRE was performed on both tumors; the other patient had IRE on one tumor and partial nephrectomy on the other. Two patients had prior nephrectomies for treatment of RCC; tumors on the remaining solitary kidney were later detected on follow-up imaging and treated with IRE. Patients with
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multiple tumors, history of renal carcinoma, or von Hippel-Lindau disease declined biopsy before treatment given the high likelihood of RCC. The locations of the tumors, creatinine values before the procedure, glomerular filtration rate values, and nephrometry scores are provided in the Table (20). Four tumors were treated in the upper pole, 10 were treated in the interpolar region, and four were treated in the lower pole.
Procedure In all cases, IRE (NanoKnife; AngioDynamics, Latham, New York) was performed percutaneously with CT guidance under general anesthesia and neuromuscular blockade. After administration of 75 mL of intravenous contrast material, the target lesion was localized. After lesion confirmation, the IRE electrodes were percutaneously introduced adjacent to the lesion with an approximate spacing of 1–2 cm between electrodes. The number of electrodes and configuration of electrode placement was determined by tumor size. For tumors o 1.5 cm in diameter, three electrodes were placed in a triangular fashion around the tumor. Larger tumors, 1.5–2.5 cm, had four electrodes placed around the tumor in a rhomboid fashion. Lesions 4 2.5 cm and approaching 4 cm required partial zonal treatments with multiple probes that were then repositioned to new locations during the procedure to ensure adequate, overlapping treatment coverage. All probes were placed in parallel in accordance with manufacturer recommendations to ensure uniform ablation. The actual electroporation was performed with cardiac synchronization. An IRE probe, 15 cm in length and 19 gauge in diameter, with exposure length of 2.0 cm was selected for the first three patients undergoing the procedure. After consultation with the manufacturer and others familiar with IRE, the exposure length was decreased to 1.5 cm. Although the shorter exposure length potentially requires probe adjustment with additional stepwise IRE ablation to ensure adequate coverage of the target lesion, it is preferred because the current density for 2.0-cm exposure (amount of electrode tip involved in actual electroporation) can be insufficient for complete cell death. In addition, longer, exposed probe lengths within surrounding fat might have altered current flow, potentially from an insulating effect. Therefore, the 1.5-cm exposure length was used for the remaining IRE procedures. To achieve adequate electroporation and irreversible damage, 30–40 A of current must pass through the tumor between electrodes. The current output is defined as a function of tissue resistance, distance between IRE probe pairs, and initial target voltage, which was set at 2,000 V/cm (12,13). After verification of electrode pair placement with CT reformatted images, a negative and positive electrode was chosen, and a 10-pulse “trial poration” or “current check” series for each probe pairing was performed.
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After the trial poration series was performed for each probe pair, voltage adjustments were made as needed. For example, if the current was o 15 A, the voltage being delivered between that particular probe pair was increased to ensure the irreversibility of the electroporation. All renal tumors were treated with the voltage pulses determined beforehand and a pulse length of 100 ms at a frequency of 1 Hz delivered for 70 bursts between each electrode pair with cardiac synchronization. After treatment between all electrode pairs, the resulting current graphs were reviewed to ensure the current increased during the ablation for each electrode pair. A current increase indicated that tissue resistance decreased secondary to the ablation (ie, the cells had been adequately electroporated). As per our institutional protocol, the polarity on the electrodes was subsequently reversed, and 70 bursts between each electrode pair were again discharged to complete the ablation. Polarity reversal is a common technique to maximize irreversible electroporation compound delivery. Because tissue heterogeneity can result in variations in current flow and regional tissue heating or desiccation, polarity reversal is hypothesized to compensate for such changes in the microenvironment and maximize cellular injury (21). Finally, a repeat CT scan with 75 mL of intravenously administered contrast material was performed to assess adequate ablation. CT was performed a few minutes after ablation with images acquired in axial planes, from 10 cm above to 10 cm below the site of ablation, with coronal reconstructions obtained. Lack of enhancing tumor was considered indicative of successful IRE ablation. After the procedure, all patients recovered in the postanesthesia care unit.
Follow-up Efficacy after the procedure was initially assessed at 6 weeks with CT or MR imaging in a renal mass protocol. CT and MR imaging were performed in multiple dynamic phases, including noncontrast, cortical, corticomedullary, and excretory phases. MR imaging sequences included T1 and T2 images, in-phase and out-of-phase imaging, and contrast-enhanced sequences. If residual enhancement (recurrence) within the tumor was identified (increase of 10 HU or intensity compared with noncontrast MR imaging), retreatment (salvage) was performed. Treatment efficacy was assessed by calculating recurrence or residual disease at follow-up intervals. Laboratory tests, including serum creatinine, were obtained at 6 weeks to evaluate potential adverse effects on renal function. Safety was assessed by calculating the incidence of complications during and after the procedure, including impact of IRE treatment on renal function. Complications were determined to be major or minor based on the Society of Interventional Radiology (SIR) classification system (22). Patients were
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followed at 6-month intervals with imaging, laboratory evaluation, and clinical examination.
Data Analysis Statistical analysis on all 20 IRE cases was performed comparing creatinine values before and after the procedure, glomerular filtration rate, age, sex, and renal nephrometry scores. Analysis was accomplished using GraphPad Prism (GraphPad Software, Inc, La Jolla, California) to perform Student t test with statistical significance set at P o .05.
RESULTS The median procedure time was 2 hours (overall room time for the patient, mean time of 2.04 h ⫾ 0.7), and a mean of 3.7 probes were used per procedure. Technical
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success was achieved in 100% of patients. Seven of 20 patients required overnight observation; two were observed for pain control, three were observed for urinary retention immediately after the procedure secondary to anesthesia, and two had resultant perinephric hematomas (minor complications). Perinephric hematomas were defined as imaging findings contained to the retroperitoneal space near the tumor that did not change after 5- to 10-minute interval repeat imaging and without decrease in blood pressure or hematocrit. No major complications were observed, as defined by the SIR guidelines on complications (22). For all patients, 6-week follow-up with imaging was available. Residual enhancement consistent with IRE failure was noted in 2 of 20 (10%) patients at 6 weeks. Both of the enhancing tumors were treated by salvage RF ablation per the treating physician’s preference and showed no evidence of recurrence 1 year after salvage
Figure 1. A 51-year-old African American woman underwent successful IRE treatment for a 1.6-cm unclassified RCC in the left interpolar region using three probes. (a) Contrast-enhanced CT image obtained before treatment demonstrates a left interpolar lesion with mild enhancement (arrow), suggestive of RCC. (b) Contrast-enhanced CT image obtained immediately after treatment demonstrates a hypodense area in the region of the tumor with mild peripheral enhancement (arrow), likely secondary to hyperemia. (c) Contrast-enhanced CT image obtained 6 months after treatment shows no evidence of enhancement in the ablation zone with a decreased size of the ablation zone. The hypodense area has become smaller (arrow) compared with the image obtained immediately after treatment. (d) Contrast-enhanced CT image obtained 1 year after ablation demonstrates no enhancement in a well-circumscribed healing area in the left kidney (arrow).
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treatment. In 15 patients (75%), 6-month follow-up with imaging was available, and 1-year follow-up imaging was available in 6 patients (30%). There was no evidence of recurrence at 6 months. At 1 year, one of six patients demonstrated recurrence and underwent a partial nephrectomy, per the patient’s preference. All three patients with IRE failure (two incomplete ablations and one recurrence) had clear cell–type RCC located in the upper pole of the kidney. No significant differences were noted in terms of creatinine levels before and after the procedure (obtained 6 weeks after the procedure) and estimated glomerular filtration rate (P 4 .05) for all patients.
Imaging Findings Figures 1a–d and Figure 2a–d demonstrate imaging findings of two patients. All 20 tumors had typical findings of renal malignancy with enhancing solid or cystic tumors within the renal parenchyma (Figs 1a, 2a). Immediately after the procedure, the ablation zone was noted to
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have had a slightly larger hypodense area compared with the lesion before the procedure. Surrounding the hypodense ablation zone, areas of enhancement in the perinephric fat likely represented hyperemia that developed after the procedure (Figs 1b, 2b). On the 6-week follow-up scans, successful ablation was demonstrated by a hypodense ablation zone that was similar in size to the original tumor. The surrounding area of enhancement seen in the scans performed after the procedure (representing hyperemia) was no longer visualized (Fig 1c). The two incomplete ablations demonstrated a margin of residual enhancing tumor consistent with viable malignancy. The ablation zone was seen as a hypodense region within the renal parenchyma on follow-up scans at 6 months. The zone showed a slight decrease in size compared with the 6-week scan, consistent with involution of the ablation zone (Figs 1c, 2c). On the 1year scan, the ablation zone was similar in size to the zone on the 6-month scan (Fig 1d). In one patient, new CT or MR imaging enhancement within the ablation zone at 1 year signaled tumor recurrence (Fig 2d).
Figure 2. A 74-year-old man underwent initial treatment with IRE for RCC. (a) Contrast-enhanced CT image obtained before treatment demonstrates an enhancing tumor in the interpolar region of the right kidney (arrow). (b) Contrast-enhanced CT image obtained immediately after treatment demonstrates hypodensity in the area of the lesion (arrow). (c) Contrast-enhanced CT image obtained 6 months after treatment demonstrates a decrease in the size of the hypodense area without enhancement (arrow); this area has shrunk compared with the image obtained immediately after treatment. (d) Gadolinium-enhanced coronal T1-weighted MR image demonstrates peripheral enhancement in the right interpolar lesion (arrow) consistent with RCC recurrence. The patient elected to undergo partial nephrectomy.
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DISCUSSION In most published studies, IRE has been performed on other organs in human patients and on porcine kidneys. The limited data published on IRE in renal tumors have demonstrated safety (13,23), but no data on clinical effectiveness have been published. This study reports our initial experience using IRE as a potential nonthermal ablation technique for selected small renal tumors (Table). All procedures were technically successful without major complications. IRE was not associated with significant change in renal function, and there was no major morbidity that resulted after the ablation procedure. Using treatment and follow-up imaging principles employed in other ablative procedures (24,25), no patient had CT or MR imaging evidence of enhancement at the 6-month follow-up, although one of six patients did have a recurrence at the 1-year scan. The imaging characteristics after IRE were similar to the characteristics observed with RF ablation and cryoablation. After IRE, renal tumors demonstrated a hypodense area that closely corresponded to the size of the tumor being treated. The hypodense area involuted after treatment in a similar time frame to that seen with cryoablation (26–28). This initial experience suggests that IRE is safe and effective in the short term for treating small renal tumors. Learning from the treatment failures, the two cases that had an incomplete ablation on the first 6-week scan occurred early in the study and, following careful review, likely resulted from probe malpositioning. Probe pairs were not optimally parallel to ensure uniform transmission of current between the probes. In the one patient with a recurrence, the recurrence site was at the interface of the tumor and renal parenchyma, as is commonly seen with other ablation modalities. The data are too immature to calculate a reliable recurrence rate for IRE, although it appears similar to reported short-term rates for RF ablation and cryoablation. For RF ablation, studies demonstrated recurrence rates at 6 months ranging from 0–20%; patients with no evidence of recurrence at 6 months showed 1-year rates of recurrence of 0–15% (10,29,30). More recent studies demonstrated a local recurrence rate of 2.5%–5% after RF ablation, with a distant metastasis rate of o 2% (31,32). Cryoablation demonstrated comparable recurrence rates at 6-month and 1-year intervals (0–20%) (10,29,30) with more recent studies reporting local recurrence rates of 3%–7% with a distant metastasis rate of o 2% (33,34). In terms of safety, RF ablation and cryoablation studies reported complications ranging from 0 to 33% depending on tumor size, with one article published in 2012 demonstrating minor complications of 0–7% (30,33). This study of IRE in renal tumors demonstrated no evidence of major complications, and 35% of patients had minor complications, suggesting IRE is as safe as RF ablation or cryoablation (35). We theorize that the lack of major complications compared with RF ablation or cryotherapy might be due to the small diameter of the IRE probe
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(19 gauge) and the IRE technique itself. However, the patient sample is small, and further study of IRE is needed. Limitations to this study include the retrospective, small experience and selection bias from inclusion of peripheral tumors distant from critical structures. A larger, prospective series with broader tumor inclusion criteria is warranted. The IRE procedure requires placement of multiple probes based on lesion location, lesion size, and presence of critical surrounding structures. Three or four probes were routinely used in our patient population, thereby creating variability as well as reliance on the skill set of the treating physician. Variables such as the number of probes, probe tip exposure, and voltage are not completely understood and require additional study to determine the most appropriate conditions for optimal ablation. Our institutional technique evolved (to use decreased exposure) during the study period and almost certainly affected outcomes. An additional limitation is the lack of long-term oncologic follow-up for the study patients, as such follow-up is necessary to fully demonstrate the efficacy of IRE. In conclusion, this study demonstrates that IRE can be safely used in the short term for treating selected small renal masses. Tumors treated with IRE demonstrated nonenhancement in the tumor bed with involution on follow-up CT or MR imaging. Larger prospective series with broader inclusion criteria and longer follow-up are essential.
REFERENCES 1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015; 65:5–29. 2. Olweny EO, Park SK, Tan YK, Best SL, Trimmer C, Cadeddu JA. Radiofrequency ablation versus partial nephrectomy in patients with solitary clinical T1a renal cell carcinoma: comparable oncologic outcomes at a minimum of 5 years of follow-up. Eur Urol 2012; 61:1156–1161. 3. Choueiri TK, Schutz FAB, Hevelone ND, et al. Thermal ablation vs surgery for localized kidney cancer: a Surveillance, Epidemiology, and End Results (SEER) Database Analysis. Urology 2011; 78:93–98. 4. Stern JM, Svatek R, Park S, et al. Intermediate comparison of partial nephrectomy and radiofrequency ablation for clinical T1a renal tumours. BJU Int 2007; 100:287–290. 5. Tracy CR, Raman JD, Donnally C, Trimmer CK, Cadeddu JA. Durable oncologic outcomes after radiofrequency ablation: experience from treating 243 small renal masses over 7.5 years. Cancer 2010; 116:3135–3142. 6. Takaki H, Yamakado K, Soga N, et al. Midterm results of radiofrequency ablation versus nephrectomy for T1a renal cell carcinoma. Jpn J Radiol 2010; 28:460–468. 7. Sung HH, Park BK, Kim CK, Choi HY, Lee HM. Comparison of percutaneous radiofrequency ablation and open partial nephrectomy for the treatment of size- and location-matched renal masses. Int J Hyperthermia 2012; 28:227–234. 8. Weizer AZ, Raj GV, O’Connell M, Robertson CN, Nelson RC, Polascik TJ. Complications after percutaneous radiofrequency ablation of renal tumors. Urology 2005; 66:1176–1180. 9. Kurup AN. Percutaneous ablation for small renal masses—complications. Semin Intervent Radiol 2014; 31:42–49. 10. Kwan KG, Matsumoto ED. Radiofrequency ablation and cryoablation of renal tumours. Curr Oncol 2007; 14:34–38. 11. Martin J, Athreya S. Meta-analysis of cryoablation versus microwave ablation for small renal masses: is there a difference in outcome? Diagn Interv Radiol (Ank) 2013; 19:501–507. 12. Olweny EO, Kapur P, Tan YK, Park SK, Adibi M, Cadeddu JA. Irreversible electroporation: evaluation of nonthermal and thermal ablative capabilities in the porcine kidney. Urology 2013; 81:679–684.
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13. Thomson KR, Cheung W, Ellis SJ, et al. Investigation of the safety of irreversible electroporation in humans. J Vasc Interv Radiol 2011; 22:611–621. 14. Kingham TP, Karkar AM, D’Angelica MI, et al. Ablation of perivascular hepatic malignant tumors with irreversible electroporation. J Am Coll Surg 2012; 215:379–387. 15. Martin RC 2nd, McFarland K, Ellis S, Velanovich V. Irreversible electroporation therapy in the management of locally advanced pancreatic adenocarcinoma. J Am Coll Surg 2012; 215:361–369. 16. Narayanan G, Hosein PJ, Arora G, et al. Percutaneous irreversible electroporation for downstaging and control of unresectable pancreatic adenocarcinoma. J Vasc Interv Radiol 2012; 23:1613–1621. 17. Silk MT, Wimmer T, Lee KS, et al. Percutaneous ablation of peribiliary tumors with irreversible electroporation. J Vasc Interv Radiol 2014; 25:112–118. 18. Usman M, Moore W, Talati R, Watkins K, Bilfinger TV. Irreversible electroporation of lung neoplasm: a case series. Med Sci Monit 2012; 18:CS43–CS47. 19. Sommer CM, Fritz S, Wachter MF, et al. Irreversible electroporation of the pig kidney with involvement of the renal pelvis: technical aspects, clinical outcome, and three-dimensional CT rendering for assessment of the treatment zone. J Vasc Interv Radiol 2013; 24:1888–1897. 20. Stevens LA, Coresh J, Feldman HI, et al. Evaluation of the modification of diet in renal disease study equation in a large diverse population. J Am Soc Nephrol 2007; 18:2749–2757. 21. Davalos RV, Mir LM, Rubinsky B. Tissue ablation with irreversible electroporation. Ann Biomed Eng 2005; 33:223–231. 22. Omary RA, Bettmann MA, Cardella JF, et al. Quality improvement guidelines for the reporting and archiving of interventional radiology procedures. J Vasc Interv Radiol 2003; 14:S293–S295. 23. Pech M, Janitzky A, Wendler JJ, et al. Irreversible electroporation of renal cell carcinoma: a first-in-man phase I clinical study. Cardiovasc Intervent Radiol 2011; 34:132–138. 24. Matsumoto ED, Watumull L, Johnson DB, et al. The radiographic evolution of radio frequency ablated renal tumors. J Urol 2004; 172: 45–48.
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25. Tan YK, Best SL, Olweny E, Park S, Trimmer C, Cadeddu JA. Radiofrequency ablation of incidental benign small renal mass: outcomes and follow-up protocol. Urology 2012; 79:827–830. 26. Kawamoto S, Solomon SB, Bluemke DA, Fishman EK. Computed tomography and magnetic resonance imaging appearance of renal neoplasms after radiofrequency ablation and cryoablation. Semin Ultrasound CT MR 2009; 30:67–77. 27. Wile GE, Leyendecker JR, Krehbiel KA, Dyer RB, Zagoria RJ. CT and MR imaging after imaging-guided thermal ablation of renal neoplasms. Radiographics 2007; 27:325–339. 28. Allen BC, Remer EM. Percutaneous cryoablation of renal tumors: patient selection, technique, and postprocedural imaging. Radiographics 2010; 30:887–900. 29. Kunkle DA, Uzzo RG. Cryoablation or radiofrequency ablation of the small renal mass. Cancer 2008; 113:2671–2680. 30. Schmit GD, Thompson RH, Kurup AN, et al. Percutaneous cryoablation of solitary sporadic renal cell carcinomas. BJU Int 2012; 110:E526–E531. 31. Psutka SP, Feldman AS, McDougal WS, McGovern FJ, Mueller P, Gervais DA. Long-term oncologic outcomes after radiofrequency ablation for T1 renal cell carcinoma. Eur Urol 2013; 63:486–492. 32. Wah TM, Irving HC, Gregory W, Cartledge J, Joyce AD, Selby PJ. Radiofrequency ablation (RFA) of renal cell carcinoma (RCC): Experience in 200 tumours. BJU Int 2014; 113:416–428. 33. Atwell TD, Schmit GD, Boorjian SA, et al. Percutaneous ablation of renal masses measuring 3.0 cm and smaller: comparative local control and complications after radiofrequency ablation and cryoablation. AJR Am J Roentgenol 2013; 200:461–466. 34. Blute JML, Okhunov Z, Moreira DM, et al. Image-guided percutaneous renal cryoablation: preoperative risk factors for recurrence and complications. BJU Int 2013; 111:E181–E185. 35. Kim HB, Sung CK, Baik KY, et al. Changes of apoptosis in tumor tissues with time after irreversible electroporation. Biochem Biophys Res Commun 2013; 435:651–656.
Minimally Invasive Percutaneous Treatment of Small Renal Tumors with Irreversible Electroporation: A Single-Center Experience Clayton K. Trimmer, DO, Ankaj Khosla, MD, Monica Morgan, MD, Summer L. Stephenson, PA-C, Asim Ozayar, MD, and Jeffrey A. Cadeddu, MD
ABSTRACT Purpose: To evaluate whether irreversible electroporation (IRE) can be used as an ablation technique for small renal tumors (T1a cancers or small benign tumors) and to describe features after ablation on computed tomography (CT) or magnetic resonance (MR) imaging. Materials and Methods: In this retrospective study, 20 patients (mean age, 65 y ⫾ 12.8 y) underwent CT-guided IRE of T1a renal carcinoma (n ¼ 13) or small benign or indeterminate renal masses o 4 cm in size (n ¼ 7). Mean tumor size was 2.2 cm ⫾ 0.7. The ablation area was verified with contrast-enhanced imaging performed immediately after the procedure to determine technical success. Imaging was performed 6 weeks (20 of 20 patients), 6 months (15 of 20), and 12 months (6 of 20) after ablation. Medical records and CT/MR imaging features of all patients were reviewed for recurrence, symptoms, and complications after treatment. Results: Technical success was achieved in all patients (100%); there were no major procedure-related complications. Minor complications occurred in 7 patients, including self-limiting perinephric hematomas, pain difficult to control, and urinary retention. Mean procedure time was 2.0 hours ⫾ 0.7. At 6 weeks, 2 patients required salvage therapy because of incomplete ablation. At 6 months, all 15 patients with imaging studies available had no evidence of recurrence. At 1 year, 1 patient (1 of 6) was noted to have experienced recurrence. CT/MR imaging after IRE ablation demonstrated an area of nonenhancement in the treatment zone that involuted over 6 months. Conclusions: Renal IRE appears to be a safe treatment for small renal tumors. Tumors treated with IRE demonstrated nonenhancement in the treatment zone with involution on follow-up CT/MR imaging.
ABBREVIATIONS IRE = irreversible electroporation, RCC = renal cell carcinoma
Renal cell carcinoma (RCC) is one of the most lethal cancers in the United States, with approximately 63,000 new cases and 13,000 deaths annually (1). Several minimally invasive techniques, such as radiofrequency (RF) ablation, cryoablation, microwave ablation, and other
From the Departments of Radiology (C.K.T., A.K., S.L.S.) and Urology (M.M., A.O., J.A.C.), University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, TX 75390. Received March 25, 2015; final revision received June 19, 2015; accepted June 20, 2015. Address correspondence to C.K.T.; E-mail: [email protected] None of the authors have identified a conflict of interest. & SIR, 2015 J Vasc Interv Radiol 2015; XX:]]]–]]] http://dx.doi.org/10.1016/j.jvir.2015.06.028
thermal ablation techniques, have been developed and implemented to treat small renal tumors (T1a renal malignancies and small benign renal tumors o 4 cm in size). Numerous studies have shown the efficacy of these techniques as equivalent to partial nephrectomy (2–7). However, thermal ablation techniques have limitations. For example, thermal ablation can damage normal, non– tumor-containing tissues surrounding the target lesion (5); of particular concern are possible injuries to critical structures such as arteries, veins, small intestine, colon, ureter, or the renal collecting system (8). Meta-analyses have shown that the most common complications from RF ablation, cryoablation, and microwave ablation are paresthesias at the probe site, vascular injury, urothelial injury (usually self-contained urinoma), and bowel injury, although together they total o 5% (9–11). Also, all
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thermal ablation technologies are less effective in treating lesions near larger blood vessels secondary to the welldocumented heat sink effect (8,11,12). Irreversible electroporation (IRE) is a newer ablation method that can be used to treat small renal masses tumors o 4 cm). Because IRE employs a nonthermal ablation, IRE could permit the treatment of tumors in close proximity to critical structures, while preserving normal renal parenchyma, with decreased complications. Clinically, IRE has been reported to be effective in the treatment of pancreatic, lung, hepatic, renal, and adrenal lesions (13–18). In terms of renal application, two studies have shown that IRE is effective and limits damage to the treatment area of the ablated lesion within porcine kidneys (12,19). The purpose of this study was to determine the clinical efficacy and safety of in situ renal tumor ablation by IRE and to describe imaging features after ablation.
MATERIALS AND METHODS All patients were counseled by their treating physician regarding management options for small renal masses, including surgery, ablation, and active surveillance, and provided written and verbal informed consent for the IRE procedure. The patients were part of an institutional review board–approved retrospective institutional renal mass database. Records of all patients who underwent IRE for treatment of small renal masses at our institution were included in this retrospective study. The selection of ablation modality was determined by the provider based on size and location. Tumors particularly close to back and paraspinal muscles were selected for IRE with the intent to reduce pain after the procedure, which often occurs with thermal ablation. Patients with nodal or distant metastases and patients with multiple tumors ipsilaterally were excluded from the study.
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Table 1 . Patient and Tumor Characteristics in Technically Successful IRE Characteristic Average age (y) Average tumor size (cm)
Value 65 ⫾ 12.8 2.2 ⫾ 0.7
Comorbidities (no. patients) Coronary artery disease Hypertension
4 10
Diabetes
7
Chronic obstructive pulmonary disease Sleep apnea
5 1
von Hippel-Lindau disease
1
Other cancer diagnosis Average operating room time (h)
3 2.0 ⫾ 0.7
No. probes
3.7 ⫾ 0.7
Histology (no. patients) Clear cell
10
Papillary
3
Oncocytoma Not available
2 5
Location (no. patients) Upper pole Interpolar Lower pole
4 10 4
Creatinine before intervention (mg/dL) Creatinine 6 wk after intervention (mg/dL)
0.99 ⫾ 0.4 0.95 ⫾ 0.2
GFR before procedure (mL/min/1.73 m2)*
73.4 ⫾ 22.2
GFR after procedure (mL/min/1.73 m2)*
73.7 ⫾ 22.8
Note–Values are given as mean ⫾ SD or number. GFR ¼ glomerular filtration rate; IRE ¼ irreversible electroporation. *Our laboratory does not specify the exact GFR when values are Z 60 mL/min/1.73 m2. The average GFR was 4 60 mL/min/ 1.73 m2 in all patients, per our laboratory, before and after the procedure. We recalculated the GFR using the Modification in Diet in Renal Disease equation to obtain an actual GFR when not stated by our laboratory (20).
Imaging and Pathologic Diagnosis Patients The study comprised 20 patients (12 women and 8 men) with a mean age of 65 years ⫾ 12.8. In 16 patients, tumors were incidentally discovered on abdominal computed tomography (CT) or magnetic resonance (MR) imaging scans. Two patients had prior partial nephrectomies and were found to have new tumors on follow-up scans. One patient with von Hippel-Lindau disease had a tumor detected on screening CT. The final patient had an immunoglobulin G deficiency, and the tumor was detected as part of routine screening CT. At the time of diagnosis, 10 of the patients had a history of hypertension. Three patients presented with a diagnosis of an additional malignancy (prostate, bladder, and colon). The remaining comorbidities are listed in the Table. All of the tumor locations were peripheral (clear of any critical structures or vessels), which allowed us to assess the possibility of IRE more safely in this early experience.
All patients underwent initial imaging, either contrastenhanced MR imaging or CT, using established institutional renal mass protocols to confirm a renal tumor. Most patients (15 of 20; 75%) had biopsy confirmation of the renal tumor before or at the time of the procedure. The average tumor size was 2.2 cm ⫾ 0.7. Tumor size was determined based on the largest diameter on CT or MR imaging performed before the procedure. A needle biopsy diagnosis was made in 15 of 20 (75%) patients; 10 were clear cell–type cancers, two were oncocytomas (detected on biopsy at the time of ablation), and three were papillary-type cancers. Two patients had bilateral renal tumors. In one case, IRE was performed on both tumors; the other patient had IRE on one tumor and partial nephrectomy on the other. Two patients had prior nephrectomies for treatment of RCC; tumors on the remaining solitary kidney were later detected on follow-up imaging and treated with IRE. Patients with
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multiple tumors, history of renal carcinoma, or von Hippel-Lindau disease declined biopsy before treatment given the high likelihood of RCC. The locations of the tumors, creatinine values before the procedure, glomerular filtration rate values, and nephrometry scores are provided in the Table (20). Four tumors were treated in the upper pole, 10 were treated in the interpolar region, and four were treated in the lower pole.
Procedure In all cases, IRE (NanoKnife; AngioDynamics, Latham, New York) was performed percutaneously with CT guidance under general anesthesia and neuromuscular blockade. After administration of 75 mL of intravenous contrast material, the target lesion was localized. After lesion confirmation, the IRE electrodes were percutaneously introduced adjacent to the lesion with an approximate spacing of 1–2 cm between electrodes. The number of electrodes and configuration of electrode placement was determined by tumor size. For tumors o 1.5 cm in diameter, three electrodes were placed in a triangular fashion around the tumor. Larger tumors, 1.5–2.5 cm, had four electrodes placed around the tumor in a rhomboid fashion. Lesions 4 2.5 cm and approaching 4 cm required partial zonal treatments with multiple probes that were then repositioned to new locations during the procedure to ensure adequate, overlapping treatment coverage. All probes were placed in parallel in accordance with manufacturer recommendations to ensure uniform ablation. The actual electroporation was performed with cardiac synchronization. An IRE probe, 15 cm in length and 19 gauge in diameter, with exposure length of 2.0 cm was selected for the first three patients undergoing the procedure. After consultation with the manufacturer and others familiar with IRE, the exposure length was decreased to 1.5 cm. Although the shorter exposure length potentially requires probe adjustment with additional stepwise IRE ablation to ensure adequate coverage of the target lesion, it is preferred because the current density for 2.0-cm exposure (amount of electrode tip involved in actual electroporation) can be insufficient for complete cell death. In addition, longer, exposed probe lengths within surrounding fat might have altered current flow, potentially from an insulating effect. Therefore, the 1.5-cm exposure length was used for the remaining IRE procedures. To achieve adequate electroporation and irreversible damage, 30–40 A of current must pass through the tumor between electrodes. The current output is defined as a function of tissue resistance, distance between IRE probe pairs, and initial target voltage, which was set at 2,000 V/cm (12,13). After verification of electrode pair placement with CT reformatted images, a negative and positive electrode was chosen, and a 10-pulse “trial poration” or “current check” series for each probe pairing was performed.
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After the trial poration series was performed for each probe pair, voltage adjustments were made as needed. For example, if the current was o 15 A, the voltage being delivered between that particular probe pair was increased to ensure the irreversibility of the electroporation. All renal tumors were treated with the voltage pulses determined beforehand and a pulse length of 100 ms at a frequency of 1 Hz delivered for 70 bursts between each electrode pair with cardiac synchronization. After treatment between all electrode pairs, the resulting current graphs were reviewed to ensure the current increased during the ablation for each electrode pair. A current increase indicated that tissue resistance decreased secondary to the ablation (ie, the cells had been adequately electroporated). As per our institutional protocol, the polarity on the electrodes was subsequently reversed, and 70 bursts between each electrode pair were again discharged to complete the ablation. Polarity reversal is a common technique to maximize irreversible electroporation compound delivery. Because tissue heterogeneity can result in variations in current flow and regional tissue heating or desiccation, polarity reversal is hypothesized to compensate for such changes in the microenvironment and maximize cellular injury (21). Finally, a repeat CT scan with 75 mL of intravenously administered contrast material was performed to assess adequate ablation. CT was performed a few minutes after ablation with images acquired in axial planes, from 10 cm above to 10 cm below the site of ablation, with coronal reconstructions obtained. Lack of enhancing tumor was considered indicative of successful IRE ablation. After the procedure, all patients recovered in the postanesthesia care unit.
Follow-up Efficacy after the procedure was initially assessed at 6 weeks with CT or MR imaging in a renal mass protocol. CT and MR imaging were performed in multiple dynamic phases, including noncontrast, cortical, corticomedullary, and excretory phases. MR imaging sequences included T1 and T2 images, in-phase and out-of-phase imaging, and contrast-enhanced sequences. If residual enhancement (recurrence) within the tumor was identified (increase of 10 HU or intensity compared with noncontrast MR imaging), retreatment (salvage) was performed. Treatment efficacy was assessed by calculating recurrence or residual disease at follow-up intervals. Laboratory tests, including serum creatinine, were obtained at 6 weeks to evaluate potential adverse effects on renal function. Safety was assessed by calculating the incidence of complications during and after the procedure, including impact of IRE treatment on renal function. Complications were determined to be major or minor based on the Society of Interventional Radiology (SIR) classification system (22). Patients were
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followed at 6-month intervals with imaging, laboratory evaluation, and clinical examination.
Data Analysis Statistical analysis on all 20 IRE cases was performed comparing creatinine values before and after the procedure, glomerular filtration rate, age, sex, and renal nephrometry scores. Analysis was accomplished using GraphPad Prism (GraphPad Software, Inc, La Jolla, California) to perform Student t test with statistical significance set at P o .05.
RESULTS The median procedure time was 2 hours (overall room time for the patient, mean time of 2.04 h ⫾ 0.7), and a mean of 3.7 probes were used per procedure. Technical
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success was achieved in 100% of patients. Seven of 20 patients required overnight observation; two were observed for pain control, three were observed for urinary retention immediately after the procedure secondary to anesthesia, and two had resultant perinephric hematomas (minor complications). Perinephric hematomas were defined as imaging findings contained to the retroperitoneal space near the tumor that did not change after 5- to 10-minute interval repeat imaging and without decrease in blood pressure or hematocrit. No major complications were observed, as defined by the SIR guidelines on complications (22). For all patients, 6-week follow-up with imaging was available. Residual enhancement consistent with IRE failure was noted in 2 of 20 (10%) patients at 6 weeks. Both of the enhancing tumors were treated by salvage RF ablation per the treating physician’s preference and showed no evidence of recurrence 1 year after salvage
Figure 1. A 51-year-old African American woman underwent successful IRE treatment for a 1.6-cm unclassified RCC in the left interpolar region using three probes. (a) Contrast-enhanced CT image obtained before treatment demonstrates a left interpolar lesion with mild enhancement (arrow), suggestive of RCC. (b) Contrast-enhanced CT image obtained immediately after treatment demonstrates a hypodense area in the region of the tumor with mild peripheral enhancement (arrow), likely secondary to hyperemia. (c) Contrast-enhanced CT image obtained 6 months after treatment shows no evidence of enhancement in the ablation zone with a decreased size of the ablation zone. The hypodense area has become smaller (arrow) compared with the image obtained immediately after treatment. (d) Contrast-enhanced CT image obtained 1 year after ablation demonstrates no enhancement in a well-circumscribed healing area in the left kidney (arrow).
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treatment. In 15 patients (75%), 6-month follow-up with imaging was available, and 1-year follow-up imaging was available in 6 patients (30%). There was no evidence of recurrence at 6 months. At 1 year, one of six patients demonstrated recurrence and underwent a partial nephrectomy, per the patient’s preference. All three patients with IRE failure (two incomplete ablations and one recurrence) had clear cell–type RCC located in the upper pole of the kidney. No significant differences were noted in terms of creatinine levels before and after the procedure (obtained 6 weeks after the procedure) and estimated glomerular filtration rate (P 4 .05) for all patients.
Imaging Findings Figures 1a–d and Figure 2a–d demonstrate imaging findings of two patients. All 20 tumors had typical findings of renal malignancy with enhancing solid or cystic tumors within the renal parenchyma (Figs 1a, 2a). Immediately after the procedure, the ablation zone was noted to
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have had a slightly larger hypodense area compared with the lesion before the procedure. Surrounding the hypodense ablation zone, areas of enhancement in the perinephric fat likely represented hyperemia that developed after the procedure (Figs 1b, 2b). On the 6-week follow-up scans, successful ablation was demonstrated by a hypodense ablation zone that was similar in size to the original tumor. The surrounding area of enhancement seen in the scans performed after the procedure (representing hyperemia) was no longer visualized (Fig 1c). The two incomplete ablations demonstrated a margin of residual enhancing tumor consistent with viable malignancy. The ablation zone was seen as a hypodense region within the renal parenchyma on follow-up scans at 6 months. The zone showed a slight decrease in size compared with the 6-week scan, consistent with involution of the ablation zone (Figs 1c, 2c). On the 1year scan, the ablation zone was similar in size to the zone on the 6-month scan (Fig 1d). In one patient, new CT or MR imaging enhancement within the ablation zone at 1 year signaled tumor recurrence (Fig 2d).
Figure 2. A 74-year-old man underwent initial treatment with IRE for RCC. (a) Contrast-enhanced CT image obtained before treatment demonstrates an enhancing tumor in the interpolar region of the right kidney (arrow). (b) Contrast-enhanced CT image obtained immediately after treatment demonstrates hypodensity in the area of the lesion (arrow). (c) Contrast-enhanced CT image obtained 6 months after treatment demonstrates a decrease in the size of the hypodense area without enhancement (arrow); this area has shrunk compared with the image obtained immediately after treatment. (d) Gadolinium-enhanced coronal T1-weighted MR image demonstrates peripheral enhancement in the right interpolar lesion (arrow) consistent with RCC recurrence. The patient elected to undergo partial nephrectomy.
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DISCUSSION In most published studies, IRE has been performed on other organs in human patients and on porcine kidneys. The limited data published on IRE in renal tumors have demonstrated safety (13,23), but no data on clinical effectiveness have been published. This study reports our initial experience using IRE as a potential nonthermal ablation technique for selected small renal tumors (Table). All procedures were technically successful without major complications. IRE was not associated with significant change in renal function, and there was no major morbidity that resulted after the ablation procedure. Using treatment and follow-up imaging principles employed in other ablative procedures (24,25), no patient had CT or MR imaging evidence of enhancement at the 6-month follow-up, although one of six patients did have a recurrence at the 1-year scan. The imaging characteristics after IRE were similar to the characteristics observed with RF ablation and cryoablation. After IRE, renal tumors demonstrated a hypodense area that closely corresponded to the size of the tumor being treated. The hypodense area involuted after treatment in a similar time frame to that seen with cryoablation (26–28). This initial experience suggests that IRE is safe and effective in the short term for treating small renal tumors. Learning from the treatment failures, the two cases that had an incomplete ablation on the first 6-week scan occurred early in the study and, following careful review, likely resulted from probe malpositioning. Probe pairs were not optimally parallel to ensure uniform transmission of current between the probes. In the one patient with a recurrence, the recurrence site was at the interface of the tumor and renal parenchyma, as is commonly seen with other ablation modalities. The data are too immature to calculate a reliable recurrence rate for IRE, although it appears similar to reported short-term rates for RF ablation and cryoablation. For RF ablation, studies demonstrated recurrence rates at 6 months ranging from 0–20%; patients with no evidence of recurrence at 6 months showed 1-year rates of recurrence of 0–15% (10,29,30). More recent studies demonstrated a local recurrence rate of 2.5%–5% after RF ablation, with a distant metastasis rate of o 2% (31,32). Cryoablation demonstrated comparable recurrence rates at 6-month and 1-year intervals (0–20%) (10,29,30) with more recent studies reporting local recurrence rates of 3%–7% with a distant metastasis rate of o 2% (33,34). In terms of safety, RF ablation and cryoablation studies reported complications ranging from 0 to 33% depending on tumor size, with one article published in 2012 demonstrating minor complications of 0–7% (30,33). This study of IRE in renal tumors demonstrated no evidence of major complications, and 35% of patients had minor complications, suggesting IRE is as safe as RF ablation or cryoablation (35). We theorize that the lack of major complications compared with RF ablation or cryotherapy might be due to the small diameter of the IRE probe
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(19 gauge) and the IRE technique itself. However, the patient sample is small, and further study of IRE is needed. Limitations to this study include the retrospective, small experience and selection bias from inclusion of peripheral tumors distant from critical structures. A larger, prospective series with broader tumor inclusion criteria is warranted. The IRE procedure requires placement of multiple probes based on lesion location, lesion size, and presence of critical surrounding structures. Three or four probes were routinely used in our patient population, thereby creating variability as well as reliance on the skill set of the treating physician. Variables such as the number of probes, probe tip exposure, and voltage are not completely understood and require additional study to determine the most appropriate conditions for optimal ablation. Our institutional technique evolved (to use decreased exposure) during the study period and almost certainly affected outcomes. An additional limitation is the lack of long-term oncologic follow-up for the study patients, as such follow-up is necessary to fully demonstrate the efficacy of IRE. In conclusion, this study demonstrates that IRE can be safely used in the short term for treating selected small renal masses. Tumors treated with IRE demonstrated nonenhancement in the tumor bed with involution on follow-up CT or MR imaging. Larger prospective series with broader inclusion criteria and longer follow-up are essential.
REFERENCES 1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015; 65:5–29. 2. Olweny EO, Park SK, Tan YK, Best SL, Trimmer C, Cadeddu JA. Radiofrequency ablation versus partial nephrectomy in patients with solitary clinical T1a renal cell carcinoma: comparable oncologic outcomes at a minimum of 5 years of follow-up. Eur Urol 2012; 61:1156–1161. 3. Choueiri TK, Schutz FAB, Hevelone ND, et al. Thermal ablation vs surgery for localized kidney cancer: a Surveillance, Epidemiology, and End Results (SEER) Database Analysis. Urology 2011; 78:93–98. 4. Stern JM, Svatek R, Park S, et al. Intermediate comparison of partial nephrectomy and radiofrequency ablation for clinical T1a renal tumours. BJU Int 2007; 100:287–290. 5. Tracy CR, Raman JD, Donnally C, Trimmer CK, Cadeddu JA. Durable oncologic outcomes after radiofrequency ablation: experience from treating 243 small renal masses over 7.5 years. Cancer 2010; 116:3135–3142. 6. Takaki H, Yamakado K, Soga N, et al. Midterm results of radiofrequency ablation versus nephrectomy for T1a renal cell carcinoma. Jpn J Radiol 2010; 28:460–468. 7. Sung HH, Park BK, Kim CK, Choi HY, Lee HM. Comparison of percutaneous radiofrequency ablation and open partial nephrectomy for the treatment of size- and location-matched renal masses. Int J Hyperthermia 2012; 28:227–234. 8. Weizer AZ, Raj GV, O’Connell M, Robertson CN, Nelson RC, Polascik TJ. Complications after percutaneous radiofrequency ablation of renal tumors. Urology 2005; 66:1176–1180. 9. Kurup AN. Percutaneous ablation for small renal masses—complications. Semin Intervent Radiol 2014; 31:42–49. 10. Kwan KG, Matsumoto ED. Radiofrequency ablation and cryoablation of renal tumours. Curr Oncol 2007; 14:34–38. 11. Martin J, Athreya S. Meta-analysis of cryoablation versus microwave ablation for small renal masses: is there a difference in outcome? Diagn Interv Radiol (Ank) 2013; 19:501–507. 12. Olweny EO, Kapur P, Tan YK, Park SK, Adibi M, Cadeddu JA. Irreversible electroporation: evaluation of nonthermal and thermal ablative capabilities in the porcine kidney. Urology 2013; 81:679–684.
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13. Thomson KR, Cheung W, Ellis SJ, et al. Investigation of the safety of irreversible electroporation in humans. J Vasc Interv Radiol 2011; 22:611–621. 14. Kingham TP, Karkar AM, D’Angelica MI, et al. Ablation of perivascular hepatic malignant tumors with irreversible electroporation. J Am Coll Surg 2012; 215:379–387. 15. Martin RC 2nd, McFarland K, Ellis S, Velanovich V. Irreversible electroporation therapy in the management of locally advanced pancreatic adenocarcinoma. J Am Coll Surg 2012; 215:361–369. 16. Narayanan G, Hosein PJ, Arora G, et al. Percutaneous irreversible electroporation for downstaging and control of unresectable pancreatic adenocarcinoma. J Vasc Interv Radiol 2012; 23:1613–1621. 17. Silk MT, Wimmer T, Lee KS, et al. Percutaneous ablation of peribiliary tumors with irreversible electroporation. J Vasc Interv Radiol 2014; 25:112–118. 18. Usman M, Moore W, Talati R, Watkins K, Bilfinger TV. Irreversible electroporation of lung neoplasm: a case series. Med Sci Monit 2012; 18:CS43–CS47. 19. Sommer CM, Fritz S, Wachter MF, et al. Irreversible electroporation of the pig kidney with involvement of the renal pelvis: technical aspects, clinical outcome, and three-dimensional CT rendering for assessment of the treatment zone. J Vasc Interv Radiol 2013; 24:1888–1897. 20. Stevens LA, Coresh J, Feldman HI, et al. Evaluation of the modification of diet in renal disease study equation in a large diverse population. J Am Soc Nephrol 2007; 18:2749–2757. 21. Davalos RV, Mir LM, Rubinsky B. Tissue ablation with irreversible electroporation. Ann Biomed Eng 2005; 33:223–231. 22. Omary RA, Bettmann MA, Cardella JF, et al. Quality improvement guidelines for the reporting and archiving of interventional radiology procedures. J Vasc Interv Radiol 2003; 14:S293–S295. 23. Pech M, Janitzky A, Wendler JJ, et al. Irreversible electroporation of renal cell carcinoma: a first-in-man phase I clinical study. Cardiovasc Intervent Radiol 2011; 34:132–138. 24. Matsumoto ED, Watumull L, Johnson DB, et al. The radiographic evolution of radio frequency ablated renal tumors. J Urol 2004; 172: 45–48.
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25. Tan YK, Best SL, Olweny E, Park S, Trimmer C, Cadeddu JA. Radiofrequency ablation of incidental benign small renal mass: outcomes and follow-up protocol. Urology 2012; 79:827–830. 26. Kawamoto S, Solomon SB, Bluemke DA, Fishman EK. Computed tomography and magnetic resonance imaging appearance of renal neoplasms after radiofrequency ablation and cryoablation. Semin Ultrasound CT MR 2009; 30:67–77. 27. Wile GE, Leyendecker JR, Krehbiel KA, Dyer RB, Zagoria RJ. CT and MR imaging after imaging-guided thermal ablation of renal neoplasms. Radiographics 2007; 27:325–339. 28. Allen BC, Remer EM. Percutaneous cryoablation of renal tumors: patient selection, technique, and postprocedural imaging. Radiographics 2010; 30:887–900. 29. Kunkle DA, Uzzo RG. Cryoablation or radiofrequency ablation of the small renal mass. Cancer 2008; 113:2671–2680. 30. Schmit GD, Thompson RH, Kurup AN, et al. Percutaneous cryoablation of solitary sporadic renal cell carcinomas. BJU Int 2012; 110:E526–E531. 31. Psutka SP, Feldman AS, McDougal WS, McGovern FJ, Mueller P, Gervais DA. Long-term oncologic outcomes after radiofrequency ablation for T1 renal cell carcinoma. Eur Urol 2013; 63:486–492. 32. Wah TM, Irving HC, Gregory W, Cartledge J, Joyce AD, Selby PJ. Radiofrequency ablation (RFA) of renal cell carcinoma (RCC): Experience in 200 tumours. BJU Int 2014; 113:416–428. 33. Atwell TD, Schmit GD, Boorjian SA, et al. Percutaneous ablation of renal masses measuring 3.0 cm and smaller: comparative local control and complications after radiofrequency ablation and cryoablation. AJR Am J Roentgenol 2013; 200:461–466. 34. Blute JML, Okhunov Z, Moreira DM, et al. Image-guided percutaneous renal cryoablation: preoperative risk factors for recurrence and complications. BJU Int 2013; 111:E181–E185. 35. Kim HB, Sung CK, Baik KY, et al. Changes of apoptosis in tumor tissues with time after irreversible electroporation. Biochem Biophys Res Commun 2013; 435:651–656.