REVIEW URRENT C OPINION
Emerging needle ablation technology in urology Raymond J. Leveillee a,b,c, Karli Pease b,c, and Nelson Salas b,c
Purpose of review Thermal ablation of urologic tumors in the form of freezing (cryoablation) and heating (radiofrequency ablation) have been utilized successfully to treat and ablate soft tissue tumors for over 15 years. Multiple studies have demonstrated efficacy nearing that of extirpative surgery for certain urologic conditions. There are technical limitations to their speed and safety profile because of the physical limits of thermal diffusion. Recent findings Recently, there has been a desire to investigate other forms of energy in an effort to circumvent the limitations of cryoblation and radiofrequency ablation. This review will focus on three relatively new energy applications as they pertain to tissue ablation: microwave, irreversible electroporation, and water vapor. High-intensity-focused ultrasound nor interstitial lasers are discussed, as there have been no recently published updates. Summary Needle and probe-based ablative treatments will continue to play an important role. As three-dimensional imaging workstations move from the advanced radiologic interventional suite to the operating room, surgeons will likely still play a pivotal role in the þ-application of these probe ablative devices. It is essential that the surgeon understands the fundamentals of these devices in order to optimize their application. Keywords ablation, electroporation, microwave, needle ablation, vapor
INTRODUCTION Urologic surgeons have often been at the forefront of surgical innovation and minimally invasive techniques. Probe ablation of urologic tissues in the form of freezing [cryoablation (CRY)] and heating [radiofrequency ablation (RFA)] have been utilized for over 15 years. Applications have been primarily directed toward the prostate gland [benign prostatic hyperplasia (BPH); prostate cancer – salvage] and the kidney (renal cancer). Although efficacious for small lesions, there are engineering challenges that manifest when trying to expand lesion sizes. Owing to variations in blood flow, lipid and salt content, and proximity to other organs, there are problems with creating overlapping spheres, and lesion sizes are limited because of thermodynamic equilibration (’you can only make the lesion so big even if you leave it on all day’) [1,2 ,3,4]. &&
Microwave The idea to use microwaves for medicinal purposes originated in Germany in 1938 (H.E. Hollman). Discussions were centered around the concept that waves could be focused to heat deep tissues with www.co-urology.com
minimal skin burning. Microwave generators were constructed but were applied to military purposes. The first therapeutic application of microwaves began at the Mayo Clinic in 1946 involving exposure of laboratory animals to 3000 MHz fields at an output power of 65 W. Most early investigations involved irradiating the surface of the subject [5]. Eventually, needle applicators were designed so that microwave energy could be delivered locally and tissues could be internally irradiated. In the late 1970s, there was an apparatus for the controlled a Department of Urology, University of Miami Miller School of Medicine, Miami, bDepartment of Biomedical Engineering, University of Miami, Coral Gables and cJoint Bioengineering and Endourology Developmental Surgical Laboratory, Department of Urology, Division of Endourology, Laparoscopy, and Minimally-Invasive Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
Correspondence to Raymond J. Leveillee, MD, FRCS-G, University of Miami Miller School of Medicine, Department of Urology, Division of Endourology, Laparoscopy, and Minimally-Invasive Surgery, 1400 NW 10th Ave, Suite 509, Miami, Florida 33136, USA. Tel: +1 305 243 4562; fax: +1 305 243 3381; e-mail: [email protected] Curr Opin Urol 2014, 24:98–103 DOI:10.1097/MOU.0000000000000017 Volume 24 Number 1 January 2014
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Emerging needle ablation technology in urology Leveillee et al.
KEY POINTS Despite the feasibility of radiofrequency ablation and cryoablation, variations in blood flow, lipid and salt content, and proximity to other organs, limit the size of ablations that can be achieved and makes control of the heating environment difficult. MWA has the advantage of a larger energy field and more direct heating compared with radiofrequency ablation, but high temperatures are induced with MWA, further necessitating studies to better control the heating. IRE is a promising, treatment modality that creates nanopores in the cell membranes by direct current pulses transferred between two electrodes, yet few clinical, urological published studies are available. The efficacy of using vapor to heat undesired tissue by utilizing the energy released from vapor during condensation has been shown for prostate and other organs outside of urology. Other investigations involving the thermal treatment of undesired masses include the combination of nanoparticles and hyperthermal ablation and the immune-modulating properties of thermal ablation.
local heating of tumors using microwave radiation in the frequency of 915 or 2450 MHz. The earliest report of microwave irradiation using a needle probe in kidneys was in 1994 in Japan [6]. Under induction of a microwave field, water molecules, which have weak unequal dipoles, attempt to orient themselves within the field. The oscillation of the electromagnetic wave between negative and positive charges causes polar molecules to rotate, generating frictional heating and coagulative necrosis when temperatures reach above 60oC. This is known as dielectric heating. Microwave energy penetration is not affected by high-temperature heating effects such as desiccation and charring as radiofrequency current or laser energy. Depth of penetration, d, is defined as the distance required for the electric field of a plane wave to attenuate to 1/e (37%) of its initial value. The depth achieved with microwave energy depends on several factors including the relative permittivity and conductivity of the tissue. These dielectric properties depend on the frequency of the microwave energy, temperature, and other factors in biological tissues, such as water content. Penetration depth of an electromagnetic field is inversely proportional to both frequency and conductivity. Balancing penetration depth and heat generation is important for evaluating which frequencies are most attractive for a given application.
Lower frequencies with slower heating rates but deeper field penetration may be more desirable for large-volume heating applications. According to Brace [7], at 915 MHz and 2.45 GHz, wave penetration is 2–4 cm in most tissues. System parameters can be adjusted on the microwave ablation (MWA) generator in order to control the ablation size (Table 1). The most common adjusted parameters are output power and irradiation time. Few systems, such as the Certus 140 and MicroThermX systems, also offer the simultaneous use of multiple probes with one generator to increase total ablation size or treat multiple tumors simultaneously. MWA offers many theoretical advantages over other needle-based ablative therapies, such as RFA and CRY. MWA has a larger zone of direct heating, and is thus less susceptible to heat sink effects because of blood flow when compared with RFA. A larger zone of heating can help to minimize desiccation and charring around the probe tip. Higher temperatures are achieved within a shorter duration, ideally resulting in a more complete and uniform zone of necrosis within shorter treatment times. Lesions tend to be teardrop or comet-shaped; thus, making perfectly spherical lesions can be complicated without the use of real-time thermography. They are simple to set up and easy to use, thus potentially allowing for shorter time in the operating room, although thus far the reported times are not dramatically shorter. No grounding pads are needed, as with RFA, and there is no need for large gas canisters, as with CRY [7,8]. Microwave transmission of energy is an interesting modality, as tissue penetration, time of application, and power can be altered to try to optimize ablation zones. Tissue characteristics (i.e., water content, fat, among others) can interfere with wave propagation; therefore, lesion symmetry can be somewhat variable. MWA is very dependent upon local water content, and should be used cautiously in organs with high water content (i.e., urinary bladder, kidney). Urological clinical studies published since 2012, according to our literature search, are limited (Table 2) [8,9 ,10 ]. Further studies during clinical applications will shed some light as to efficacy and/or superiority over other ablation modalities. &&
&
Irreversible electroporation Irreversible electroporation (IRE) is a minimally invasive treatment modality that utilizes electricity to ablate tissue in a nonthermal fashion. IRE uses an electric field, resultant of the transmission of direct current pulses between two electrodes, to create nanopores in the cell membranes, which increase
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New technologies in urology Table 1. Currently available microwave systems System
Frequency
Power
Time
Antenna(e)
Evident, Covidien, Mansfield, Massachusetts
915 MHz
Up to 45 W
0–10 min
13 G, 2.0 and 3.7 cm emitting length, 12–22 cm shaft length, saline solution cooling
MicrothermX, BSD Medical, Salt Lake City, Utah
915 MHz
180 W, 60 W per channel maximum
0–10 min
14 G, 2.0 and 4.1 cm emitting length, up to three antennas, saline solution cooling
Avecure, Medwaves, San Diego, California
902–928 MHz
10–32 W (power or temp mode); reflection monitoring, temperature monitoring
0–15 min
12–16 G, 1–4 cm emitting length, 7–30 cm shaft length; no cooling required
Acculis MTA, Microsulis, Hampshire, England
2450 MHz
30–180 W; reflection monitoring
0 to 8 min
1.8 and 5.6-mm diameter, 1.4 cm emitting length, ceramic trocar cutting tip, 14–33.4 cm shaft length; saline solution cooling
Amica, Hospital Service, Rome, Italy
2450 MHz
Up to 100 W; reflection monitoring
Up to 10 min
11, 14, and 16 G, 2 cm emitting length, with miniaturized choke
Certus 140, Neuwied, Madison, Wisconsin
2450 MHz
Up to 140 W on single channel, 65 W each on three channels
Up to 10 min
17 G, 1–2 cm emitting length, tri-axial probes, 15–20 mm shaft length, gas cooled
Information on these systems are either available on the manufacturers’ websites or were given word of mouth to the authors.
the permeability of the cell. It is theorized that the change in the cell transmembrane potential because of the induced electrical field either opens existing ion channels or forms nanoscale pores throughout the cell membrane. This leads to the loss of homeostasis and eventual cell death [11,12]. The kidney is a heterogeneous organ and results from IRE in kidney may be different than in homogenous organs such as breast and liver. In fact, several investigators have recently studied these effects, but to date, there are no large, short, or medium-term follow-up studies available. The same is true for the prostate. After initially, very promising results in 2008, there has only recently been a randomized trial. Despite recent, promising experimental studies [13–18,19 ], there are currently no recent published data regarding prostate cancer, and only two articles since 2011 regarding renal tumors (Table 3) [20,21]. We await further studies to be able to make some comments about interpretation. As more experience is gained and the possibility of improved precision exists, IRE may have an increased role in the urologists’ probe ablation armamentarium. &
Vapor Thermal water vapor is a new energy source that is being used in the human body for therapeutic applications outside of Urology. Some of these include lung volume reduction for emphysema [22], endometrial ablation, uterine fibroids [23], and varicose vein reduction. Early clinical experience has been gained in the treatment of BPH and prostate cancer [24,25 ]. To date, there is no experimental or clinical evidence of efficacy on renal tissues. &
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Thermal VAP is a highly controlled production and application of steam. There is a tremendous amount of stored potential thermal energy in VAP that releases to tissue when condensation (i.e., a phase shift from gas to liquid) occurs. Unlike the previously mentioned ablation modalities, this system incorporates a molecular-level transfer of thermal energy. The application time to produce enough thermal energy in a volume of tissue follows a typical bell-shaped thermal diffusion curve. Application of VAP into tissue, however, works by distributing the thermal energy through convection. Convection is the transfer of heat through mass flow, as in the bulk movement of a liquid, gas. or vapor. The more vapor that is injected per unit time, the farther the vapor moves interstitially into the tissue and therefore the greater the volume of tissue that gets treated. Unlike thermal diffusion, treatment of a specific volume of tissue with VAP convection occurs within seconds instead of minutes when treated with the aforementioned thermal modalities. RFA is limited by the vaporization of tissue at temperatures exceeding 1008C and the subsequent change in impedance associated with carbonization – which acts like an insulating blanket – so that only a limited amount of power may be applied to the tissue. Even though microwave penetration during MWA may not be highly affected by carbonization, the heat distribution may be inhibited, with a rapid temperature rise within the charred tissue while minimizing heat conduction to adjacent tissue. Heat distribution via water vapor is not as limited by the thermal conductivity of tissue as RFA and MWA are. Because vapor is a bulk flow of wet, high thermal energy content media, it does not desiccate and thermally fix the tissue, resulting in the body Volume 24 Number 1 January 2014
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KY2000 (Kangyou Medical Instruments, Nanjing, China), single 15-gauge cooled shaft antenna, 2450 MHz
AMICA (Hospital Services Spa, Aprilia, Italy), single V4 applicator, 2450 MHz
Valley Lab Evident (Covidien Inc.,Valleylab, Boulder, CO), two 13-gauge, 3.7 cm surgical antennae, 915 MHz
Guan et al. [8]
Bartoletti et al. && [9 ]
Castle et al. & [10 ] 1
14
48
4.33 cm
Mean: 4.7 1.87 cm (4.0–9.2)
Mean: 3.1 0.8 (1.2–3.9)
Mean tumor size (range)
Laparoscopic (US)
Open
Open (US) or laparoscopic (US)
Approach (guidance)
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Ultrasound
Ultrasound and/or CT
Pech et al. [20]
Thomson et al. [21]
CT, computed tomography; IRE, irreversible electroporation.
Guidance/approach
Study
Seven (10 tumors)
Six (three male, three female, age ¼ 43.5–73.1 years)
Patient/ablation amount
1.6–4.5 cm
20–39 mm
4.3 months
1 and 3 months
Ablate and resects
CT scan performed at 4.3 months showed nodular thickening with enhancement at the ablation site, RFA salvage performed
PNx performed after all ablations
Single treatment: 1 year, 100%; 2 year, 95.1%; 3 year, 93.3%
Recurrence-free success
Complete ablation in five of seven patients (two required second IRE procedure)
1–3 positioning of the needles were required. All lesions encompassed tumor prior to resection.
Overall success rate
Mean: 27.4 4.2 months
Median: 32 months (24–54)
Mean/median follow-up (range)
Mean follow-up time
Oncology: 1 and 4.3 months
Not specified
Oncology: 1, 3 and 6 months, 1 year, and every 6 months thereafter
Follow-up
Mean tumor size
Table 3. Kidney: published results using irreversible electroporation (Nanoknife)
MWA, microwave ablation; RFA, radiofrequency ablation; CT, computed tomography.
System, frequency
Authors
Table 2. Summary of clinical microwave ablation data (last 18 months)
Transient hematuria in two patients extending into central portion of the kidney. Coagulative necrosis with one patient at biopsy. One patient with partial ureteric obstruction, which may be the result of previous radiofrequency ablation.
One case of intraoperative supraventricular extrasystole
Complication rate
Case study of re-ablation of tumor using RFA after MWA failure
Tumor ablated prior to removing kidney via open partial nephrectomy
Two patients underwent re-ablation after 1-month follow-up. CT showed incomplete ablation, no disease-specific deaths
Comments
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New technologies in urology
almost completely removing the treated tissue within weeks of application. There are very little data published on this extremely novel technology. A preliminary study involving anticoagulated rabbits demonstrated superiority in terms of blood loss during controlled renal ablations in sham vs. RFA vs ‘vapor’ [26]. In a periprostatectomy study, 11 patients diagnosed with BPH and with median lobes were treated with 2.2 injections of thermal water vapor into each lateral lobe. The median lobes were treated with an average of 2.1 injections each. An adenectomy was performed on these patients and treated with tetrazolium stain (a vital dye). The lesions identified had a diameter range of 2.2–4.3 cm and were contained within the prostate transition zones. The lesions within the lateral lobes were observed to coalesce and were contiguous from the base to the apical end of the transition zone. The mean volume of ablated lesions ranged from 4.72–6.61 cm3 for lateral lobes and 2.9 cm3 for the median lobes. SEM images of excised adenomas showed distinct demarcations between necrosed and viable prostate tissue. The tissue interstices were observed to have expanded in the treated areas. This helps demonstrate the dispersion of vapor into and through the prostate tissue where condensation occurs and the thermal energy is released. Histology showed the cell membranes of the necrosed tissue were denatured and disrupted as opposed to the smooth and orderly structure of viable tissue. In a chronic study, 30 patients were treated with thermal water vapor and were evaluated 1 week post-treatment with gadolinium-enhanced MRIs to assess volume and location of the ablative lesions. The MRIs were analyzed by the Mayo Clinic Image Analysis Center using Analyze 10.1 software. Gadolinium MRI imaging of the patients showed prostate defects in all glands and they were contiguous, coalesced lesions in the lateral lobes corresponding to vapor injection locations. At 1 week, the mean volume of gadolinium defects was 9.5 cm3. Patient with a large prostate (167 g) was treated with a higher dose of vapor and had a defect volume of 35.1 cm3. The convective dispersion of vapor through prostate tissue interstices, as demonstrated on SEM images, creates therapeutic temperatures on the surface of the cell membranes resulting in lesions as seen in post-treatment histological and radiographic images. MRI images also demonstrate that vapor injected into the prostate transition zone does not leave that zone convectively and stays within the psuedocapsule. The images also show that vapor injected in 9 s does not thermally diffuse or conduct outside the psuedocapsule of the transition zone or the prostatic capsule [24,25 ]. &
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Sterile thermal water vapor is a unique thermodynamic energy source that when injected into the prostatic tissue distributes rapidly via convection. It uses less than 0.5 ml of sterile water that is converted to vapor, and then condenses back to water when it contacts body temperature tissue. The cellular membrane treatment and subsequent cell death result in complete and homogenous treatments within the treated zone. Vapor has the ability to rapidly and controllably treat large volumes of tissue in a short period of time.
FUTURE OUTLOOK Evaluation of combined use of nanoparticles and hyperthermal ablation is being performed to assess whether this combination therapy will augment the efficacy of thermoablative treatments [27]. Simultaneously there is continued interest in evaluating the immune-modulating properties of thermal ablation [28]. These initiatives aim to establish the full potential of thermoablative therapy.
CONCLUSION Novel ablation technologies, including MWA and IRE among others, have undergone preliminary preclinical and clinical evaluation. Further refinement and assessment of outcomes is required prior to routine clinical use for urologic tumor ablation. Acknowledgements The authors would like to thank Michael Hoey, PhD (Chief Technology Officer, NxThera, Inc., Minneapolis, MN) for his description of Water Vapor effect on tissues and for sharing his insight. Source of Funding: none. Conflicts of interest Disclosure: The authors have a relationship with Medwaves, Incorporated, San Diego, CA, USA (supply of research equipment) and Microsulis, UK (lab equiptment – no financial support), which had no bearing on the content of this review.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Castro A Jr, Jenkins L, Ekwenna O, et al. Instrumentation and technique: hyperthermal ablation: radiofrequency and microwave ablation. In: Monga M, Rane A, editors. Percutaneous renal surgery. West Sussex, UK: Wiley-Blackwell; 2013.
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Emerging needle ablation technology in urology Leveillee et al. 2. Castro A Jr, Jenkins LC, Salas N, et al. Ablative therapies for small renal tumours. Nat Rev Urol 2013; 10:284–291. This is a review of the current and experimental modalities that are currently available for the treatment of small renal tumors. The methodology, advantages, and disadvantage of RFA, MWA, CRA, IRE, laser ablation, and high-intensityfocused ultrasound were described. Oncological outcomes for small renal masses were described for RFA and CRY. 3. Ramanathan R, Leveillee RJ. Ablative therapies for renal tumors. Ther Adv Urol 2010; 2:51–68. 4. Young EE, Castle SM, Gorbatiy V, Leveillee RJ. Comparison of safety, renal function outcomes and efficacy of laparoscopic and percutaneous radio frequency ablation of renal masses. J Urol 2012; 187:1177–1182. 5. Guy A. History of biological effects and medical applications of microwaveenergy. IEEE Transactions on Microwave Theory and Techniques 1984; 32:1182–1200. 6. Kigure T, Harada T, Yuri Y, et al. Experimental study of microwave coagulation of a vx-2 carcinoma implanted in rabbit kidney. Int J Urol 1994; 1:23–27. 7. Brace CL. Microwave tissue ablation: biophysics, technology, and applications. Crit Rev Biomed Eng 2010; 38:65–78. 8. Guan W, Bai J, Liu J, et al. Microwave ablation versus partial nephrectomy for small renal tumors: Intermediate-term results. J Surg Oncol 2012; 106:316– 321. 9. Bartoletti R, Meliani E, Simonato A, et al. Microwave-induced thermoablation && with amica-probe is a safe and reproducible method to treat solid renal masses: results from a phase I study. Oncol Rep 2012; 28:1243–1248. The objective of this article was to compare the surgical outcomes of patients treated with MWA with those treated with partial nephrectomy (PNx) for small renal masses. For this study, 102 patients (54 with PNx, 48 with MWA) treated for a solitary renal mass and with at least 2 years of follow-up (mean ¼ 36 and 32 months, respectively) were chosen retrospectively. Surgical and hospitalization time were comparable. Blood loss, complication rate, and decline of postoperative renal function were significantly less for MWA patients. Three-year recurrence-free survival rates, according to Kaplan–Meier estimates, are 96% and 91.3% for PNx and MWA, respectively. These results prove that for at least 2 years after follow-up, patients treated with MWA for a solitary tumor had similar or enhanced surgical outcomes to PNx. 10. Castle SM, Salas N, Leveillee RJ. Radio-frequency ablation helps preserve & nephrons in salvage of failed microwave ablation for a renal cancer in a solitary kidney. Urol Ann 2013; 5:42–44. Energy ablative treatment modalities are considered a viable alternative for patients with solitary kidneys presented with a small renal mass. In this case study, a 63-year-old male presented with a 4.33-cm mass on his solitary kidney. Recurrence was observed at 4.3-month follow-up after MWA. No recurrence was observed at 11-month follow-up after salvage RFA. A 15% decrease in GFR was observed throughout this ordeal. Owing to the sparing of nephrons and minimal trauma, there was small change in the patient’s renal function. 11. Davalos RV, Mir LM, Rubinsky B. Tissue ablation with irreversible electroporation. Ann Biomed Eng 2005; 33:223–231. 12. Esser AT, Smith KC, Gowrishankar TR, Weaver JC. Towards solid tumor treatment by irreversible electroporation: intrinsic redistribution of fields and currents in tissue. Technol Cancer Res Treat 2007; 6:261–273. 13. Ben-David E, Ahmed M, Faroja M, et al. Irreversible electroporation: treatment effect is susceptible to local environment and tissue properties. Radiology 2013; E-pub ahead of print. 14. Neal RE II, Garcia PA, Robertson JL, Davalos RV. Experimental characterization and numerical modeling of tissue electrical conductivity during pulsed electric fields for irreversible electroporation treatment planning. IEEE Transactions on Biomedical Engineering 2012; 59:1076–1085. &&
15. Olweny EO, Kapur P, Tan YK, et al. Irreversible electroporation: evaluation of nonthermal and thermal ablative capabilities in the porcine kidney. Urology 2013; 81:679–684. 16. van den Bos W, Muller BG, de la Rosette JJCMH. A randomized controlled trial on focal therapy for localized prostate carcinoma: hemiablation versus complete ablation with irreversible electroporation. J Endourol 2013; 27:262–264. 17. Wendler JJ, Pech M, Blaschke S, et al. Angiography in the isolated perfused kidney: radiological evaluation of vascular protection in tissue ablation by nonthermal irreversible electroporation. Cardiovasc Intervent Radiol 2012; 35:383–390. 18. Wendler JJ, Pech M, Porsch M, et al. Urinary tract effects after multifocal nonthermal irreversible electroporation of the kidney: acute and chronic monitoring by magnetic resonance imaging, intravenous urography and urinary cytology. Cardiovasc Intervent Radiol 2012; 35:921–926. 19. Wendler JJ, Porsch M, Huhne S, et al. Short- and mid-term effects of & irreversible electroporation on normal renal tissue: an animal model. Cardiovasc Intervent Radiol 2013; 36:512–520. This study demonstrated the effect of IRE in the normal kidney. Percutaneous IRE was performed in the right kidney of three swine (2–3 per kidney, 8 lesions total). MRI was performed between 30 min and 28 days postoperatively. A clear boundary was observed between the lesion and the surrounding normal parenchyma through MRI. Cortical glomeruli and tubules were destroyed, but the collecting ducts, calyxes, and medullary pelvis were preserved. This signifies that IRE can be beneficial for those tumors near the collecting system and the hilum. 20. 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. 21. Thomson KR, Cheung W, Ellis SJ, et al. Investigation of the safety of irreversible electroporation in humans. J Vasc Intervent Radiol 2011; 22:611–621. 22. Henne E, Anderson J, Barry R, Kesten S. Thermal effect of endoscopic thermal vapour ablation on the lung surface in human ex vivo tissue. Int J Hyperthermia 2012; 28:466–472. 23. Jessop M, Chill N, Coad J. Successful vapor-based endometrial ablation: in vivo peri-hysterectomy study. J Minim Invasive Gynecol 2011; 18:445–448. 24. Dixon C, Huidobro C, Rijo Cedano E, et al. Acute effects in the human prostate following treatment with high-calorie water vapor (RezumTM). J Endourol 2012; 26:A403. 25. Dixon CM, Huidobro C, Cedano ER, et al. Preliminary data following treatment & with vapor for BPH: The RezumTM System. J Endourol 2012; 26:A270. Vapor technology is an up and coming modality for the treatment of undesired tissue. A preliminary, IRB-approved investigation to determine the efficacy of the RexumTM vapor ablation system was performed on 18 patients with BPH. One to three ablations were performed per lateral lobe for 7–10 s depending on the prostate volume (mean ¼ 44 cc, range ¼ 24–108 cc). MRI was performed 1 week postoperatively. Lesions that are 1.8–2.5 cm in diameter were created with no outside damage. Patients had minimal discomfort throughout the procedure and suffered minimal frequency, urgency dysuria. 26. Ball A, Leveillee R, Hoey M, et al. Estimation of acute blood loss in the anticoagulated rabbit model using 3 modalities of radiofrequency energy ablation. J Urol 2003; 170:970–974. 27. Manthe RL, Foy SP, Krishnamurthy N, et al. Tumor ablation and nanotechnology. Mol Pharm 2010; 7:1880–1898. 28. Haen SP, Pereira PL, Salih HR, et al. More than just tumor destruction: immunomodulation by thermal ablation of cancer. Clin Dev Immunol 2011; 2011:160250.
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Emerging needle ablation technology in urology Raymond J. Leveillee a,b,c, Karli Pease b,c, and Nelson Salas b,c
Purpose of review Thermal ablation of urologic tumors in the form of freezing (cryoablation) and heating (radiofrequency ablation) have been utilized successfully to treat and ablate soft tissue tumors for over 15 years. Multiple studies have demonstrated efficacy nearing that of extirpative surgery for certain urologic conditions. There are technical limitations to their speed and safety profile because of the physical limits of thermal diffusion. Recent findings Recently, there has been a desire to investigate other forms of energy in an effort to circumvent the limitations of cryoblation and radiofrequency ablation. This review will focus on three relatively new energy applications as they pertain to tissue ablation: microwave, irreversible electroporation, and water vapor. High-intensity-focused ultrasound nor interstitial lasers are discussed, as there have been no recently published updates. Summary Needle and probe-based ablative treatments will continue to play an important role. As three-dimensional imaging workstations move from the advanced radiologic interventional suite to the operating room, surgeons will likely still play a pivotal role in the þ-application of these probe ablative devices. It is essential that the surgeon understands the fundamentals of these devices in order to optimize their application. Keywords ablation, electroporation, microwave, needle ablation, vapor
INTRODUCTION Urologic surgeons have often been at the forefront of surgical innovation and minimally invasive techniques. Probe ablation of urologic tissues in the form of freezing [cryoablation (CRY)] and heating [radiofrequency ablation (RFA)] have been utilized for over 15 years. Applications have been primarily directed toward the prostate gland [benign prostatic hyperplasia (BPH); prostate cancer – salvage] and the kidney (renal cancer). Although efficacious for small lesions, there are engineering challenges that manifest when trying to expand lesion sizes. Owing to variations in blood flow, lipid and salt content, and proximity to other organs, there are problems with creating overlapping spheres, and lesion sizes are limited because of thermodynamic equilibration (’you can only make the lesion so big even if you leave it on all day’) [1,2 ,3,4]. &&
Microwave The idea to use microwaves for medicinal purposes originated in Germany in 1938 (H.E. Hollman). Discussions were centered around the concept that waves could be focused to heat deep tissues with www.co-urology.com
minimal skin burning. Microwave generators were constructed but were applied to military purposes. The first therapeutic application of microwaves began at the Mayo Clinic in 1946 involving exposure of laboratory animals to 3000 MHz fields at an output power of 65 W. Most early investigations involved irradiating the surface of the subject [5]. Eventually, needle applicators were designed so that microwave energy could be delivered locally and tissues could be internally irradiated. In the late 1970s, there was an apparatus for the controlled a Department of Urology, University of Miami Miller School of Medicine, Miami, bDepartment of Biomedical Engineering, University of Miami, Coral Gables and cJoint Bioengineering and Endourology Developmental Surgical Laboratory, Department of Urology, Division of Endourology, Laparoscopy, and Minimally-Invasive Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA
Correspondence to Raymond J. Leveillee, MD, FRCS-G, University of Miami Miller School of Medicine, Department of Urology, Division of Endourology, Laparoscopy, and Minimally-Invasive Surgery, 1400 NW 10th Ave, Suite 509, Miami, Florida 33136, USA. Tel: +1 305 243 4562; fax: +1 305 243 3381; e-mail: [email protected] Curr Opin Urol 2014, 24:98–103 DOI:10.1097/MOU.0000000000000017 Volume 24 Number 1 January 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Emerging needle ablation technology in urology Leveillee et al.
KEY POINTS Despite the feasibility of radiofrequency ablation and cryoablation, variations in blood flow, lipid and salt content, and proximity to other organs, limit the size of ablations that can be achieved and makes control of the heating environment difficult. MWA has the advantage of a larger energy field and more direct heating compared with radiofrequency ablation, but high temperatures are induced with MWA, further necessitating studies to better control the heating. IRE is a promising, treatment modality that creates nanopores in the cell membranes by direct current pulses transferred between two electrodes, yet few clinical, urological published studies are available. The efficacy of using vapor to heat undesired tissue by utilizing the energy released from vapor during condensation has been shown for prostate and other organs outside of urology. Other investigations involving the thermal treatment of undesired masses include the combination of nanoparticles and hyperthermal ablation and the immune-modulating properties of thermal ablation.
local heating of tumors using microwave radiation in the frequency of 915 or 2450 MHz. The earliest report of microwave irradiation using a needle probe in kidneys was in 1994 in Japan [6]. Under induction of a microwave field, water molecules, which have weak unequal dipoles, attempt to orient themselves within the field. The oscillation of the electromagnetic wave between negative and positive charges causes polar molecules to rotate, generating frictional heating and coagulative necrosis when temperatures reach above 60oC. This is known as dielectric heating. Microwave energy penetration is not affected by high-temperature heating effects such as desiccation and charring as radiofrequency current or laser energy. Depth of penetration, d, is defined as the distance required for the electric field of a plane wave to attenuate to 1/e (37%) of its initial value. The depth achieved with microwave energy depends on several factors including the relative permittivity and conductivity of the tissue. These dielectric properties depend on the frequency of the microwave energy, temperature, and other factors in biological tissues, such as water content. Penetration depth of an electromagnetic field is inversely proportional to both frequency and conductivity. Balancing penetration depth and heat generation is important for evaluating which frequencies are most attractive for a given application.
Lower frequencies with slower heating rates but deeper field penetration may be more desirable for large-volume heating applications. According to Brace [7], at 915 MHz and 2.45 GHz, wave penetration is 2–4 cm in most tissues. System parameters can be adjusted on the microwave ablation (MWA) generator in order to control the ablation size (Table 1). The most common adjusted parameters are output power and irradiation time. Few systems, such as the Certus 140 and MicroThermX systems, also offer the simultaneous use of multiple probes with one generator to increase total ablation size or treat multiple tumors simultaneously. MWA offers many theoretical advantages over other needle-based ablative therapies, such as RFA and CRY. MWA has a larger zone of direct heating, and is thus less susceptible to heat sink effects because of blood flow when compared with RFA. A larger zone of heating can help to minimize desiccation and charring around the probe tip. Higher temperatures are achieved within a shorter duration, ideally resulting in a more complete and uniform zone of necrosis within shorter treatment times. Lesions tend to be teardrop or comet-shaped; thus, making perfectly spherical lesions can be complicated without the use of real-time thermography. They are simple to set up and easy to use, thus potentially allowing for shorter time in the operating room, although thus far the reported times are not dramatically shorter. No grounding pads are needed, as with RFA, and there is no need for large gas canisters, as with CRY [7,8]. Microwave transmission of energy is an interesting modality, as tissue penetration, time of application, and power can be altered to try to optimize ablation zones. Tissue characteristics (i.e., water content, fat, among others) can interfere with wave propagation; therefore, lesion symmetry can be somewhat variable. MWA is very dependent upon local water content, and should be used cautiously in organs with high water content (i.e., urinary bladder, kidney). Urological clinical studies published since 2012, according to our literature search, are limited (Table 2) [8,9 ,10 ]. Further studies during clinical applications will shed some light as to efficacy and/or superiority over other ablation modalities. &&
&
Irreversible electroporation Irreversible electroporation (IRE) is a minimally invasive treatment modality that utilizes electricity to ablate tissue in a nonthermal fashion. IRE uses an electric field, resultant of the transmission of direct current pulses between two electrodes, to create nanopores in the cell membranes, which increase
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New technologies in urology Table 1. Currently available microwave systems System
Frequency
Power
Time
Antenna(e)
Evident, Covidien, Mansfield, Massachusetts
915 MHz
Up to 45 W
0–10 min
13 G, 2.0 and 3.7 cm emitting length, 12–22 cm shaft length, saline solution cooling
MicrothermX, BSD Medical, Salt Lake City, Utah
915 MHz
180 W, 60 W per channel maximum
0–10 min
14 G, 2.0 and 4.1 cm emitting length, up to three antennas, saline solution cooling
Avecure, Medwaves, San Diego, California
902–928 MHz
10–32 W (power or temp mode); reflection monitoring, temperature monitoring
0–15 min
12–16 G, 1–4 cm emitting length, 7–30 cm shaft length; no cooling required
Acculis MTA, Microsulis, Hampshire, England
2450 MHz
30–180 W; reflection monitoring
0 to 8 min
1.8 and 5.6-mm diameter, 1.4 cm emitting length, ceramic trocar cutting tip, 14–33.4 cm shaft length; saline solution cooling
Amica, Hospital Service, Rome, Italy
2450 MHz
Up to 100 W; reflection monitoring
Up to 10 min
11, 14, and 16 G, 2 cm emitting length, with miniaturized choke
Certus 140, Neuwied, Madison, Wisconsin
2450 MHz
Up to 140 W on single channel, 65 W each on three channels
Up to 10 min
17 G, 1–2 cm emitting length, tri-axial probes, 15–20 mm shaft length, gas cooled
Information on these systems are either available on the manufacturers’ websites or were given word of mouth to the authors.
the permeability of the cell. It is theorized that the change in the cell transmembrane potential because of the induced electrical field either opens existing ion channels or forms nanoscale pores throughout the cell membrane. This leads to the loss of homeostasis and eventual cell death [11,12]. The kidney is a heterogeneous organ and results from IRE in kidney may be different than in homogenous organs such as breast and liver. In fact, several investigators have recently studied these effects, but to date, there are no large, short, or medium-term follow-up studies available. The same is true for the prostate. After initially, very promising results in 2008, there has only recently been a randomized trial. Despite recent, promising experimental studies [13–18,19 ], there are currently no recent published data regarding prostate cancer, and only two articles since 2011 regarding renal tumors (Table 3) [20,21]. We await further studies to be able to make some comments about interpretation. As more experience is gained and the possibility of improved precision exists, IRE may have an increased role in the urologists’ probe ablation armamentarium. &
Vapor Thermal water vapor is a new energy source that is being used in the human body for therapeutic applications outside of Urology. Some of these include lung volume reduction for emphysema [22], endometrial ablation, uterine fibroids [23], and varicose vein reduction. Early clinical experience has been gained in the treatment of BPH and prostate cancer [24,25 ]. To date, there is no experimental or clinical evidence of efficacy on renal tissues. &
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Thermal VAP is a highly controlled production and application of steam. There is a tremendous amount of stored potential thermal energy in VAP that releases to tissue when condensation (i.e., a phase shift from gas to liquid) occurs. Unlike the previously mentioned ablation modalities, this system incorporates a molecular-level transfer of thermal energy. The application time to produce enough thermal energy in a volume of tissue follows a typical bell-shaped thermal diffusion curve. Application of VAP into tissue, however, works by distributing the thermal energy through convection. Convection is the transfer of heat through mass flow, as in the bulk movement of a liquid, gas. or vapor. The more vapor that is injected per unit time, the farther the vapor moves interstitially into the tissue and therefore the greater the volume of tissue that gets treated. Unlike thermal diffusion, treatment of a specific volume of tissue with VAP convection occurs within seconds instead of minutes when treated with the aforementioned thermal modalities. RFA is limited by the vaporization of tissue at temperatures exceeding 1008C and the subsequent change in impedance associated with carbonization – which acts like an insulating blanket – so that only a limited amount of power may be applied to the tissue. Even though microwave penetration during MWA may not be highly affected by carbonization, the heat distribution may be inhibited, with a rapid temperature rise within the charred tissue while minimizing heat conduction to adjacent tissue. Heat distribution via water vapor is not as limited by the thermal conductivity of tissue as RFA and MWA are. Because vapor is a bulk flow of wet, high thermal energy content media, it does not desiccate and thermally fix the tissue, resulting in the body Volume 24 Number 1 January 2014
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KY2000 (Kangyou Medical Instruments, Nanjing, China), single 15-gauge cooled shaft antenna, 2450 MHz
AMICA (Hospital Services Spa, Aprilia, Italy), single V4 applicator, 2450 MHz
Valley Lab Evident (Covidien Inc.,Valleylab, Boulder, CO), two 13-gauge, 3.7 cm surgical antennae, 915 MHz
Guan et al. [8]
Bartoletti et al. && [9 ]
Castle et al. & [10 ] 1
14
48
4.33 cm
Mean: 4.7 1.87 cm (4.0–9.2)
Mean: 3.1 0.8 (1.2–3.9)
Mean tumor size (range)
Laparoscopic (US)
Open
Open (US) or laparoscopic (US)
Approach (guidance)
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Ultrasound
Ultrasound and/or CT
Pech et al. [20]
Thomson et al. [21]
CT, computed tomography; IRE, irreversible electroporation.
Guidance/approach
Study
Seven (10 tumors)
Six (three male, three female, age ¼ 43.5–73.1 years)
Patient/ablation amount
1.6–4.5 cm
20–39 mm
4.3 months
1 and 3 months
Ablate and resects
CT scan performed at 4.3 months showed nodular thickening with enhancement at the ablation site, RFA salvage performed
PNx performed after all ablations
Single treatment: 1 year, 100%; 2 year, 95.1%; 3 year, 93.3%
Recurrence-free success
Complete ablation in five of seven patients (two required second IRE procedure)
1–3 positioning of the needles were required. All lesions encompassed tumor prior to resection.
Overall success rate
Mean: 27.4 4.2 months
Median: 32 months (24–54)
Mean/median follow-up (range)
Mean follow-up time
Oncology: 1 and 4.3 months
Not specified
Oncology: 1, 3 and 6 months, 1 year, and every 6 months thereafter
Follow-up
Mean tumor size
Table 3. Kidney: published results using irreversible electroporation (Nanoknife)
MWA, microwave ablation; RFA, radiofrequency ablation; CT, computed tomography.
System, frequency
Authors
Table 2. Summary of clinical microwave ablation data (last 18 months)
Transient hematuria in two patients extending into central portion of the kidney. Coagulative necrosis with one patient at biopsy. One patient with partial ureteric obstruction, which may be the result of previous radiofrequency ablation.
One case of intraoperative supraventricular extrasystole
Complication rate
Case study of re-ablation of tumor using RFA after MWA failure
Tumor ablated prior to removing kidney via open partial nephrectomy
Two patients underwent re-ablation after 1-month follow-up. CT showed incomplete ablation, no disease-specific deaths
Comments
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New technologies in urology
almost completely removing the treated tissue within weeks of application. There are very little data published on this extremely novel technology. A preliminary study involving anticoagulated rabbits demonstrated superiority in terms of blood loss during controlled renal ablations in sham vs. RFA vs ‘vapor’ [26]. In a periprostatectomy study, 11 patients diagnosed with BPH and with median lobes were treated with 2.2 injections of thermal water vapor into each lateral lobe. The median lobes were treated with an average of 2.1 injections each. An adenectomy was performed on these patients and treated with tetrazolium stain (a vital dye). The lesions identified had a diameter range of 2.2–4.3 cm and were contained within the prostate transition zones. The lesions within the lateral lobes were observed to coalesce and were contiguous from the base to the apical end of the transition zone. The mean volume of ablated lesions ranged from 4.72–6.61 cm3 for lateral lobes and 2.9 cm3 for the median lobes. SEM images of excised adenomas showed distinct demarcations between necrosed and viable prostate tissue. The tissue interstices were observed to have expanded in the treated areas. This helps demonstrate the dispersion of vapor into and through the prostate tissue where condensation occurs and the thermal energy is released. Histology showed the cell membranes of the necrosed tissue were denatured and disrupted as opposed to the smooth and orderly structure of viable tissue. In a chronic study, 30 patients were treated with thermal water vapor and were evaluated 1 week post-treatment with gadolinium-enhanced MRIs to assess volume and location of the ablative lesions. The MRIs were analyzed by the Mayo Clinic Image Analysis Center using Analyze 10.1 software. Gadolinium MRI imaging of the patients showed prostate defects in all glands and they were contiguous, coalesced lesions in the lateral lobes corresponding to vapor injection locations. At 1 week, the mean volume of gadolinium defects was 9.5 cm3. Patient with a large prostate (167 g) was treated with a higher dose of vapor and had a defect volume of 35.1 cm3. The convective dispersion of vapor through prostate tissue interstices, as demonstrated on SEM images, creates therapeutic temperatures on the surface of the cell membranes resulting in lesions as seen in post-treatment histological and radiographic images. MRI images also demonstrate that vapor injected into the prostate transition zone does not leave that zone convectively and stays within the psuedocapsule. The images also show that vapor injected in 9 s does not thermally diffuse or conduct outside the psuedocapsule of the transition zone or the prostatic capsule [24,25 ]. &
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Sterile thermal water vapor is a unique thermodynamic energy source that when injected into the prostatic tissue distributes rapidly via convection. It uses less than 0.5 ml of sterile water that is converted to vapor, and then condenses back to water when it contacts body temperature tissue. The cellular membrane treatment and subsequent cell death result in complete and homogenous treatments within the treated zone. Vapor has the ability to rapidly and controllably treat large volumes of tissue in a short period of time.
FUTURE OUTLOOK Evaluation of combined use of nanoparticles and hyperthermal ablation is being performed to assess whether this combination therapy will augment the efficacy of thermoablative treatments [27]. Simultaneously there is continued interest in evaluating the immune-modulating properties of thermal ablation [28]. These initiatives aim to establish the full potential of thermoablative therapy.
CONCLUSION Novel ablation technologies, including MWA and IRE among others, have undergone preliminary preclinical and clinical evaluation. Further refinement and assessment of outcomes is required prior to routine clinical use for urologic tumor ablation. Acknowledgements The authors would like to thank Michael Hoey, PhD (Chief Technology Officer, NxThera, Inc., Minneapolis, MN) for his description of Water Vapor effect on tissues and for sharing his insight. Source of Funding: none. Conflicts of interest Disclosure: The authors have a relationship with Medwaves, Incorporated, San Diego, CA, USA (supply of research equipment) and Microsulis, UK (lab equiptment – no financial support), which had no bearing on the content of this review.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Castro A Jr, Jenkins L, Ekwenna O, et al. Instrumentation and technique: hyperthermal ablation: radiofrequency and microwave ablation. In: Monga M, Rane A, editors. Percutaneous renal surgery. West Sussex, UK: Wiley-Blackwell; 2013.
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Emerging needle ablation technology in urology Leveillee et al. 2. Castro A Jr, Jenkins LC, Salas N, et al. Ablative therapies for small renal tumours. Nat Rev Urol 2013; 10:284–291. This is a review of the current and experimental modalities that are currently available for the treatment of small renal tumors. The methodology, advantages, and disadvantage of RFA, MWA, CRA, IRE, laser ablation, and high-intensityfocused ultrasound were described. Oncological outcomes for small renal masses were described for RFA and CRY. 3. Ramanathan R, Leveillee RJ. Ablative therapies for renal tumors. Ther Adv Urol 2010; 2:51–68. 4. Young EE, Castle SM, Gorbatiy V, Leveillee RJ. Comparison of safety, renal function outcomes and efficacy of laparoscopic and percutaneous radio frequency ablation of renal masses. J Urol 2012; 187:1177–1182. 5. Guy A. History of biological effects and medical applications of microwaveenergy. IEEE Transactions on Microwave Theory and Techniques 1984; 32:1182–1200. 6. Kigure T, Harada T, Yuri Y, et al. Experimental study of microwave coagulation of a vx-2 carcinoma implanted in rabbit kidney. Int J Urol 1994; 1:23–27. 7. Brace CL. Microwave tissue ablation: biophysics, technology, and applications. Crit Rev Biomed Eng 2010; 38:65–78. 8. Guan W, Bai J, Liu J, et al. Microwave ablation versus partial nephrectomy for small renal tumors: Intermediate-term results. J Surg Oncol 2012; 106:316– 321. 9. Bartoletti R, Meliani E, Simonato A, et al. Microwave-induced thermoablation && with amica-probe is a safe and reproducible method to treat solid renal masses: results from a phase I study. Oncol Rep 2012; 28:1243–1248. The objective of this article was to compare the surgical outcomes of patients treated with MWA with those treated with partial nephrectomy (PNx) for small renal masses. For this study, 102 patients (54 with PNx, 48 with MWA) treated for a solitary renal mass and with at least 2 years of follow-up (mean ¼ 36 and 32 months, respectively) were chosen retrospectively. Surgical and hospitalization time were comparable. Blood loss, complication rate, and decline of postoperative renal function were significantly less for MWA patients. Three-year recurrence-free survival rates, according to Kaplan–Meier estimates, are 96% and 91.3% for PNx and MWA, respectively. These results prove that for at least 2 years after follow-up, patients treated with MWA for a solitary tumor had similar or enhanced surgical outcomes to PNx. 10. Castle SM, Salas N, Leveillee RJ. Radio-frequency ablation helps preserve & nephrons in salvage of failed microwave ablation for a renal cancer in a solitary kidney. Urol Ann 2013; 5:42–44. Energy ablative treatment modalities are considered a viable alternative for patients with solitary kidneys presented with a small renal mass. In this case study, a 63-year-old male presented with a 4.33-cm mass on his solitary kidney. Recurrence was observed at 4.3-month follow-up after MWA. No recurrence was observed at 11-month follow-up after salvage RFA. A 15% decrease in GFR was observed throughout this ordeal. Owing to the sparing of nephrons and minimal trauma, there was small change in the patient’s renal function. 11. Davalos RV, Mir LM, Rubinsky B. Tissue ablation with irreversible electroporation. Ann Biomed Eng 2005; 33:223–231. 12. Esser AT, Smith KC, Gowrishankar TR, Weaver JC. Towards solid tumor treatment by irreversible electroporation: intrinsic redistribution of fields and currents in tissue. Technol Cancer Res Treat 2007; 6:261–273. 13. Ben-David E, Ahmed M, Faroja M, et al. Irreversible electroporation: treatment effect is susceptible to local environment and tissue properties. Radiology 2013; E-pub ahead of print. 14. Neal RE II, Garcia PA, Robertson JL, Davalos RV. Experimental characterization and numerical modeling of tissue electrical conductivity during pulsed electric fields for irreversible electroporation treatment planning. IEEE Transactions on Biomedical Engineering 2012; 59:1076–1085. &&
15. Olweny EO, Kapur P, Tan YK, et al. Irreversible electroporation: evaluation of nonthermal and thermal ablative capabilities in the porcine kidney. Urology 2013; 81:679–684. 16. van den Bos W, Muller BG, de la Rosette JJCMH. A randomized controlled trial on focal therapy for localized prostate carcinoma: hemiablation versus complete ablation with irreversible electroporation. J Endourol 2013; 27:262–264. 17. Wendler JJ, Pech M, Blaschke S, et al. Angiography in the isolated perfused kidney: radiological evaluation of vascular protection in tissue ablation by nonthermal irreversible electroporation. Cardiovasc Intervent Radiol 2012; 35:383–390. 18. Wendler JJ, Pech M, Porsch M, et al. Urinary tract effects after multifocal nonthermal irreversible electroporation of the kidney: acute and chronic monitoring by magnetic resonance imaging, intravenous urography and urinary cytology. Cardiovasc Intervent Radiol 2012; 35:921–926. 19. Wendler JJ, Porsch M, Huhne S, et al. Short- and mid-term effects of & irreversible electroporation on normal renal tissue: an animal model. Cardiovasc Intervent Radiol 2013; 36:512–520. This study demonstrated the effect of IRE in the normal kidney. Percutaneous IRE was performed in the right kidney of three swine (2–3 per kidney, 8 lesions total). MRI was performed between 30 min and 28 days postoperatively. A clear boundary was observed between the lesion and the surrounding normal parenchyma through MRI. Cortical glomeruli and tubules were destroyed, but the collecting ducts, calyxes, and medullary pelvis were preserved. This signifies that IRE can be beneficial for those tumors near the collecting system and the hilum. 20. 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. 21. Thomson KR, Cheung W, Ellis SJ, et al. Investigation of the safety of irreversible electroporation in humans. J Vasc Intervent Radiol 2011; 22:611–621. 22. Henne E, Anderson J, Barry R, Kesten S. Thermal effect of endoscopic thermal vapour ablation on the lung surface in human ex vivo tissue. Int J Hyperthermia 2012; 28:466–472. 23. Jessop M, Chill N, Coad J. Successful vapor-based endometrial ablation: in vivo peri-hysterectomy study. J Minim Invasive Gynecol 2011; 18:445–448. 24. Dixon C, Huidobro C, Rijo Cedano E, et al. Acute effects in the human prostate following treatment with high-calorie water vapor (RezumTM). J Endourol 2012; 26:A403. 25. Dixon CM, Huidobro C, Cedano ER, et al. Preliminary data following treatment & with vapor for BPH: The RezumTM System. J Endourol 2012; 26:A270. Vapor technology is an up and coming modality for the treatment of undesired tissue. A preliminary, IRB-approved investigation to determine the efficacy of the RexumTM vapor ablation system was performed on 18 patients with BPH. One to three ablations were performed per lateral lobe for 7–10 s depending on the prostate volume (mean ¼ 44 cc, range ¼ 24–108 cc). MRI was performed 1 week postoperatively. Lesions that are 1.8–2.5 cm in diameter were created with no outside damage. Patients had minimal discomfort throughout the procedure and suffered minimal frequency, urgency dysuria. 26. Ball A, Leveillee R, Hoey M, et al. Estimation of acute blood loss in the anticoagulated rabbit model using 3 modalities of radiofrequency energy ablation. J Urol 2003; 170:970–974. 27. Manthe RL, Foy SP, Krishnamurthy N, et al. Tumor ablation and nanotechnology. Mol Pharm 2010; 7:1880–1898. 28. Haen SP, Pereira PL, Salih HR, et al. More than just tumor destruction: immunomodulation by thermal ablation of cancer. Clin Dev Immunol 2011; 2011:160250.
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