Cryoablation for small renal tumors: Current status and future perspectives

Urologic Oncology: Seminars and Original Investigations 30 (2012) S20 –S27

Article

Cryoablation for small renal tumors: Current status and future perspectives Riccardo Autorino, M.D., Jihad H. Kaouk, M.D.* Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA

Abstract The aim of the present review is to summarize the current status and provide future perspectives of cryotherapy in the management of small renal masses. Cryotechnology is rapidly developing and cryosurgery can nowadays offer the advantage of combining a nephronsparing surgery together with a minimally invasive approach. Given appropriate patient selection, kidney cryoablation shows encouraging intermediate term oncologic outcomes. Major recent advances have been made towards more accurate probe positioning, increased energy delivery, and reduced treatment-related morbidity. © 2012 Elsevier Inc. All rights reserved. Keywords: Cryotherapy; Kidney cancer; Nephron-sparing surgery; Focal therapy; Thermal ablation

Introduction The estimated increase in the incidence of renal cell carcinoma (RCC) over the last 2 decades has been largely due to the improved detection of localized tumors as small renal masses (SRMs) in asymptomatic patients [1]. In managing patients with SRMs, 3 competing factors are usually considered: cancer control, patient morbidity, and preservation of renal function. Nephron-sparing surgery currently represents the mainstay of treatment for such SRMs. Active surveillance is considered an appropriate strategy for elderly patients or patients with significant comorbidities who are not good surgical candidates. In high-risk patients, thermal ablative treatment modalities have been applied for selected cases with the potential benefits of decreased morbidity [2]. Several ablative technologies that have been investigated either clinically or experimentally include cryoablation [3], radiofrequency ablation [4], high-intensity focused ultrasound [5], microwave thermotherapy [6], and chemo-ablation [7]. Clinically, cryo- and radiofrequency ablation represent the 2 modalities currently used in the treatment of SRMs and are considered as an option in selected cases in current clinical guidelines [8,9]. Disclosure/Conflict of Interest Statement: R. Autorino and J.H. Kaouk have no disclosures. * Corresponding author. Tel.: ⫹1-216-444-2976; fax: ⫹1-216-4457031. E-mail address: [email protected] (J.H. Kaouk). 1078-1439/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.urolonc.2011.10.012

First described by Uchida et al. in 1995 [10], cryoablation represents the most applied and studied of all ablative modalities. It derives its tumoricidal effects from intracellular ice formation and delayed microcirculatory failure and is currently performed by 1 of 2 main minimally invasive approaches: laparoscopic and percutaneous [11]. Over the last years, a resurgence of visceral cryosurgery has been driven by the development of improved cryodelivery systems and cryoprobes and intra- and postoperative imaging systems. In the present review, we summarize the current status and provide future perspectives of cryotherapy in the management of SRMs.

Principles of cryobiology The exact mechanism of tissue injury leading to cell death during cryotherapy remains to be fully elucidated. Animal studies have shown that the tissue effects of cryosurgery can generally be classified as immediate and delayed. Acute tissue injury results from ice formation in tissues. Initial ice formation occurs in the extracellular space because the lipid bilayer in cellular membranes inhibits crystal growth. Extracellular ice formation increases the osmotic concentration and causes movement of water from inside the cells to the extracellular compartment. This eventually leads to changes in intracellular solute composition, pH, and protein denaturation. Further, extracellular ice crys-

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Double freeze-thaw cycle Rapid freeze - Slow thaw

Tumoricidal cascade after Cryotherapy ACUTE EVENTS

CHRONIC EVENTS

FREEZE

THAW

INTRAVASCULAR ICE FORMATION & VASOCONSTRICTION

EXTRACELLULAR ICE FORMATION WITH HYPERTONICITY

EXTRACELLULAR HYPOTONICITY

ENDOTHELIAL CELL DESTRUCTION

FLUID SHIFT WITH INTRACELLULAR DEHYDRATATION

FLUID SHIFT BACK TO INTRACELLULAR COMPARTMENT

PLATELET AGGREGATION

INTRACELLULAR ICE FORMATION

CELLULAR SWELLING

INTRAVASCULAR MICROTHROMBI

Disruption of intracellular organelles & cell membrane

Cellular rupture

Tissue ischemia

Fig. 1. Tumoricidal cascade after cryotherapy. (Color version of figure is available online.)

tal formation may cause mechanical disruption of the cell membranes and, hence, intracellular ice formation. Delayed tissue injury occurs in the hours and days after cryoablation and is the result of indirect damage to the microvasculature of the target tissue. One of the first tissue components affected by freezing is small blood vessels that expand, thus causing damage to endothelial cells. Endothelial dysfunction leads to edema and stimulation of platelet aggregation, which results in vascular thrombosis and tissue necrosis. This combination of vascular events leads to delayed cell death and probably represents the most important killing mechanism that occurs during cryosurgery. Immunologic changes associated with freezing and thawing may serve as an additional source of cell death (Figure 1) [12–15]. During renal cryotherapy, tumor destruction occurs through rapid freeze–thaw cycles, and 2 freeze–thaw cycles appear to achieve the best tissue ablation. Cryotherapy aims to decrease the target tissue temperature to below the level that correlates with complete necrosis. Chosy et al. found that renal tissue required exposure to a temperature of ⱕ –9.4°C [16]. This work was substantiated by Campbell et al., who observed complete necrosis 3.1 mm inside the edge of the ice ball, this physical location correlating with a temperature of –19.4°C [17]. Clinical protocols generally freeze to – 40°C. Such a temperature end point can be determined by placement of thermocouples at the tumor margin; alternatively, ultrasound can be used to verify extension of the ice ball 1 cm beyond the margin of the tumor [14].

Liquid argon and liquid nitrogen are the 2 most commonly used cryogens.

Surgical technique Cryosurgery targets the same amount of tumoral tissue that would be removed if a conventional surgical excision were performed. To achieve this, the ice ball is expected to extend a minimum of 5 mm beyond the tumor edge whenever possible [11]. This is also dictated by the location of the mass in relation to surrounding structures. The treatment plan is made by performing a CT before the ablation. The choice of a laparoscopic or percutaneous approach is mainly based on tumor location: tumors located anteriorly or medially in close proximity to bowel or adjacent organs typically are managed by laparoscopic approach, and tumors that are oriented more posteriorly and laterally by percutaneous approach. Laparoscopic cryoablation Laparoscopic cryoablation allows precise cryoprobe positioning and monitoring of the evolving ice ball under real-time ultrasonic and visual control. General anesthesia and overnight hospital stay are required. This technique has been previously described in detail [18]. Briefly, the patient is placed in the flank position. The abdomen is insufflated, and the laparoscope inserted. Adhesions are dissected care-

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fully and the colon is reflected medially to expose the kidney. The tumor location is confirmed by intraoperative ultrasound. Tru-Cut needle biopsy is then performed under ultrasound guidance. One or more probes are then inserted into the center of the tumor and freezing is started. After 2 freeze cycles, the probe is removed and the ablation zone is monitored for subsequent hemorrhage. Post-thaw hemostasis is secured by using argon-beam coagulation and/or applying hemostatic agents, such as FloSeal (Baxter Healthcare SA, Zurich, Switzerland), and Surgicel (Ethicon, Somerville, NJ). Percutaneous cryoablation Percutaneous cryoablation is appealing when the targeted mass is accessible away from bowel and vital organs such as pancreas, gallbladder, or great vessels. Conscious sedation with local anesthesia is mostly used when the cryoablation is performed percutaneously, allowing the procedure to be an outpatient setting. A detailed technique has been previously described [19]. Briefly, just before the ablation, a Chiba biopsy needle is passed under CT fluoroscopic guidance into the mass in order to obtain a fine needle aspiration (FNA) for pathology. The use of FNA in the case of percutaneous procedures is done with the aim of minimizing the risk of hemorrhagic complications as we cannot count on hemostatic agents. Even if limitations related to the use of FNA, such as false negatives or ‘non-diagnostic’ samples, are to be considered, the indication for cryoablation is based on a radiologic diagnosis. The cryoprobe (Endocare, Irvine, CA) measuring 1.7 or 2.4 mm is inserted, under i.v. sedation and local anesthesia, percutaneously into the center of the mass with the tip going just beyond the margin of the mass. Two cycles of cryoablation are then performed, with the first cycle usually lasting for 10 minutes and the second for 8 –10 minutes. Passive thaw is performed between the ablation cycles and active thaw after the second. CT scan is usually performed late in the first ablation cycle to document the size and coverage of the ice ball. A final CT scan is performed after removal of the probes to evaluate for potential hematoma.

Follow-up While partial nephrectomy can rely on pathology exam of the tumor plus subsequent radiologic imaging, ablation techniques primarily rely on radiologic exam to determine treatment success. For cryotherapy, loss of enhancement and decreased size represent the 2 primary components of a successful ablation. Ideally, following CA, there is no enhancement within the ablation zone. Central enhancement at any point time and rim enhancement after 1 year is worrisome for recurrence [20].

No standard protocol for imaging follow-up of ablated lesions currently exists. Our follow-up protocol includes a combination of MRI scans and needle-biopsy in order to maximize the chances for early detection of any tumor recurrence. CT-guided needle biopsy of the cryolesion is usually performed 6 months postoperatively. This is based on evidence that non-enhancing post-ablation treatment zone on early imaging studies might still harbor viable tumor cells [21]. In addition, enhancing areas within ablation zones do not always represent residual cancer on pathologic analysis [22]. Nevertheless, it should be recognized that evidence on the value of post-ablation biopsy remains contradictory and an optimal biopsy protocol remains to be determined. CT or MRI imaging of the cryolesion is tentatively obtained on postoperative day 1, to rule out immediate postoperative complications, and at 3, 6, 12, 18, 24, 36, 48, and 60 months. An identical surveillance protocol is maintained in the case of non-diagnostic biopsies and “normal renal tissue” biopsies as cases of patients recurring with RCC after an originally “negative” biopsy are possible.

Oncologic outcomes Overall, the majority of studies evaluating outcomes following renal tumor cryoablation consists of single-institution reports with relatively limited patient numbers and follow-up. Only few laparoscopic series have matured intermediate follow-up data (Table 1) [23–29]. Overall, cryoablation can offer a durable treatment in the majority of patients who undergo the procedure, although local recurrence rate, which is significantly higher than exenterative procedures (e.g., partial nephrectomy). Indeed, current guidelines list cryotherapy as an “option,” not the “standard” treatment as partial nephrectomy still remains the gold standard in the appropriate patient [8,9]. Data comparing percutaneous and laparoscopic cryotherapy techniques have only recently begun to emerge. Percutaneous cryoablation has been shown to be more costeffective and to result in a shorter convalescence [30,31]. Regarding oncologic efficacy between the 2 techniques, to date, comparative assessments are also mostly limited to small single-institution reports. In a multicenter comparative analysis, Strom et al. evaluated 61 patients treated by percutaneous and matched them with 84 patients treated by laparoscopic cryotherapy. Mean follow-up was 31 and 42 months, respectively. A higher rate of local tumor recurrence was noted in the percutaneous group (16.4 % vs. 5.9%), even if no significant difference was found in terms of disease-free and overall survival [32]. A recent pooled analysis by Long et al. including 42 studies suggested that cryoablation provides similar oncologic outcomes regardless of the approach [33].

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Table 1 Oncological outcomes of kidney cryoablation: An overview of selected case series Reference

Patients (masses), n

Approach

Tumor size, cm

Biopsy-proven RCC, % of masses

Follow-up, months

CSS, %

Hegarty [23] Guazzoni [24] Beemster [25] Aron [26] Tsivian [27] Atwell [28] Vricella [29]

84 123 92 80 163 91 52

Lap Lap Lap Lap Lap Perc Perc

2.3 2.1 (median) 2.5 (mean) 2.3 (median) 2.4 (mean) 3.4 (mean) 2.5 (mean)

67 65.8 51 69 72.4 60 52

82 (median) 46 (mean) 30 (mean) 93 (median) 20 (median) 26 (mean) 21 (mean)

95 100 100 92 100 100 100

RCC ⫽ renal cell carcinoma; CSS ⫽ cancer-specific survival.

Functional outcomes

tion at midterm follow-up and that in patients with chronic renal insufficiency, it offers excellent preservation of renal function [35]. We recently assessed the outcomes of computerized tomography guided percutaneous cryotherapy of kidney tumors in patients with a solitary kidney. Twenty- nine patients were analyzed with a median follow-up of 15.1 months. Two-year actuarial overall, cancer specific, recurrence-free, and metastasis-free survival rates were 89%, 100%, 69%, and 86%, respectively. No significant decrease in renal functional parameters was found at the latest follow-up visit [36]. We also evaluated the efficacy and safety of probe ablative therapy as salvage treatment for renal

Renal function outcomes after renal cryosurgery have not been widely scrutinized (Table 2). Malcolm et al. recently reported the 2-year renal function outcomes from a single-center cohort of 62 patients characterized by highly prevalent medical comorbidities and treated by laparoscopic and percutaneous renal cryoablation. Mean follow-up was 30 months and mean tumor size was 2.3 cm. Renal function was generally well maintained, with a low rate of de novo chronic kidney disease [34]. Similarly, Tsivian et al concluded that only a minimal decline in renal function is appreciated in patients undergoing laparoscopic cryoablaTable 2 Functional outcomes of kidney cryoablation: an overview of selected case series Reference

Patients, n

Age, years

Malcolm [34]

62

67

Tsivian [35]

67

64–69

Altunrende [36]

29a

62.8

Yang [37]

14b

45c

Tumor size, cm

Approach

Length of follow-up, months

Change in renal function

Progression to ESRD, n

2.3

Lap and Perc

30

0

2–2.5

Lap

20.5–24.3

2.4

Perc

17

2.64

Lap and Perc

37.6

Mean change in eGFR ⫺12.8ml/min/1.73 m2. De novo CKD noted in 5 of 45 (11%) patients. Average time to development of de novo CKD 11.4 months eGFR decreased by approximately 5ml/min/ 1.73 m2 eGFR statistically significantly reduced compared with preoperative values at all time points considered with a median reduction of 4.2 to 4.6 ml/min/1.73 m2 in CKD and up to 8.7 ml/min/1.73 m2 in normal renal function patients. Distributions of CKD categories at all time similar to preoperative Latest mean eGFR 54.2 ml/min/1.73 m2. No significant difference between preoperative and latest eGFR No significant decline of renal function up to 3 months postoperatively. Significant decline detected thereafter (mean baseline eGFR 61 ml/min vs. mean latest eGFR 51.7 ml/min, P ⬍ 0.038)

0

0

0

Values expressed as means unless otherwise specified. CKD ⫽ chronic kidney disease category 3 or higher, i.e., eGFR ⬍ 60 ml/min/1.73 m2; ESRD ⫽ end stage renal disease requiring dyalisis; na ⫽ not available. a Solitary kidneys. b VHL patients. c Median.

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Table 3 Complications of kidney cryoablation: an overview of selected case series Reference

Procedures, n

Study design

Approach

Overall complications, n (%)

Major complications, n (%)

Most common complications

Johnson [38] Tsivian [39] Laguna [40]

139 195 148

Multicenter Single center Multicenter

Lap and Perc Lap and Perc Lap and Open

30 (11.1) 36 (18.4) 23 (15.5)

5 (1.8) 7 (3.6) 6 (4.1)

Pain/paraesthesia at probe insertion site Pain/paraesthesia at probe insertion site Ileus

tumor in von Hippel-Lindau patients after previous partial nephrectomy. Tumors were ablated by either percutaneous cryoablation (n ⫽ 13) and laparoscopic cryoablation (n ⫽ 3). All procedures were successfully completed without complications. Postoperative decline in renal function was minimal and not clinically significant [37].

Complications Overall, cryoablation is well tolerated. Its most common sequelae are self-limited pain and parasthesia at the sites of probe insertion. Other rare complications include hemorrhage, infection, visceral injury, pneumothorax, and delayed UPJ obstruction [11]. Few large studies specifically looking at complications associated with cryoablation have been reported so far (Table 3). In a multi-institutional study evaluating complications after 139 cryoablation procedures, 2 major and 18 minor complications were reported [38]. The only major complication in the laparoscopic group was open conversion during a procedure due to inability to access the tumor. Urinary fistulae due to collecting-system injury after renal cryoablation are rare. Among 179 renal tumors treated at Cleveland Clinic by using laparoscopic cryoablation, 11 complications were observed [19]. Three major complications included hemothorax, congestive heart failure, and myocardial infarction.

Tsivian et al. recently reported on postoperative complications associated with cryotherapy in a single tertiary center experience. A total of 195 patients were included in the analysis (72 underwent laparoscopic and 123 percutaneous cryotherapy). Complications were observed in 14% of laparoscopic cases and 21% of percutaneous ones (P ⫽ 0.253). The distribution of the complications differed significantly between the groups, with mild complications more common in the percutaneous group (20.3% vs. 5.6%) and severe events more frequent in the laparoscopic group (8.3% vs. 0.8%). On multivariate analysis, the chosen ablative approach (laparoscopic or percutaneous) was not associated with the risk of complications [39]. Laguna et al. have collected a multi-institutional European experience with 144 patients treated with ultrathin probes. Using strict criteria show a 15% complication rate, of which 50% were relatively minor complications (not requiring surgical, endoscopic, or radiographic intervention) [40].

Recent advances and future perspectives In the effort of improving the outcome and reducing the morbidity associated with cryoablative procedures, major recent advances have been made towards 3 main directions: more accurate probe positioning, increased energy delivery and reduced treatment-related morbidity (Table 4) [41].

Table 4 Ongoing research in renal cryotherapy: An overview (adapted from [35]) Technique [ref.]

Setting

Anesthesia

Potential indication (tumor location)

Claimed advantages

Current limitations

RVS [42,43]

Pre-clinical Clinical

Conscious sedation

Posterior

Immature data

CT-Nav [44]

Clinical

Conscious sedation

Posterior

SPARC [45]

Clinical

General

Anterior, posterior

Precise percutaneous cryoprobe placement. Shorter radiation exposure Precise percutaneous cryoprobe placement. Shorter radiation exposure Virtually scar less procedure

NOTES [47]

Preclinical

General

Anterior, posterior

Scarless procedure

Immature data

Better ergonomics and instrument maneuverability needed For posterior masses unlikely to be less invasive than percutaneous approach Lack of suitable instrumentation, including specific NOTES cryoprobe

SPARC ⫽ single port access renal cryoablation; RVS ⫽ real-time virtual ultrasonography; NOTES ⫽ natural orifice translumenal endoscopic surgery.

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Fig. 2. Percutaneous cryoprobe placement under stereotactic surgical navigation guidance with CT-Nav (Koelis, France). Probe guide is tracked by infrared sensors to synchronize the probe position with preloaded CT scan of the patient. (Color version of figure is available online.)

Real-time virtual ultrasonography (RVS) Although US may have the ability to monitor real time probe placement and formation of cryolesion, the quality of image is not optimal and sometimes shadowed with ribcage or cryoprobe itself. As such, a reliable real time imaging modality still remains to be found. RVS (Hitachi Medical Corporation, Tokyo, Japan) represents a new technology allowing the fusion of real-time US and preoperative CT data. RVS displays the synchronized pictures of both real-time US and preoperative CT of the same section of the body, displayed on a split screen, simultaneously [40]. Haber et al. investigated the accuracy of percutaneous cryoablation for kidney tumors performed under combined real-time ultrasound and 3D CT scan navigation with the RVS imaging system in a porcine model [43]. Stereotactic surgical navigation CT-Nav (Koelis, La Tronche, France) represents a novel stereotactic surgical navigation system allowing precise percutaneous cryoprobe placement while reducing radiation exposure compared with conventional CT-guided procedures (Figure 2). A prospective pilot study was performed to evaluate the technical feasibility, safety, and accuracy of the CT-Nav system during renal cryoablation [42]. Patients with enhancing renal masses amenable to renal cryoablation underwent preoperative CT scan with a preplaced tracking sensor taped to the body of the patient. Using a stereroscopic infrared camera, the tracking sensor was located

three-dimensionally and a tracking handle used to guide the cryoprobe percutaneously based on the preoperative preloaded CT-scan. Immediately following cryoprobe placement, a CT-scan was repeated to confirm placement accuracy. A total of 13 tumors (mean size 2.2 cm) in 10 patients successfully underwent cryoablation using the novel navigational system. Mean operative time was 155 minutes. No intraoperative or postoperative complications were noted. Mean length of stay was 9.5 hours. Mean targeting registration error was 4.2 mm. Single port access renal cryoablation (SPARC) In an attempt to decrease number of laparoscopic ports used, we recently reported our initial experience with single port laparoscopic approach [45]. Patients with localized small renal mass (⬍3 cm) ineligible for partial or radical nephrectomy were included. A multichannel single port was positioned in the umbilicus during the transperitoneal approach and at the tip of the 12th rib during the retroperitoneal approach. Intraoperative biopsy was performed and a 3.8-mm cryoprobe (Endocare, Inc., Irvine, CA) was inserted under ultrasound guidance through 1 of the multichannel working ports. Two freeze-thaw cryoablation cycles were performed. All 6 cases (mean tumor size 2.6), 4 retroperitoneal and 2 transperitoneal, underwent SPARC without conversion to laparoscopy or open surgery. No intraoperative complications were noted and mean hospital stay was 2.3 days. CT with contrast documented no residual tumor enhancement in 3 cases. In this early experience we found SPARC to be feasible and safe, allowing a virtually scarless surgical procedure.

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Natural orifice translumenal endoscopic surgery Natural orifice translumenal endoscopic surgery (NOTES) is an emerging minimally invasive surgical technique with significant ongoing investigation [46]. Our group presented an early experience with transgastric and transvaginal NOTES renal cryoablation in a porcine model for anteriorly located renal tumors not accessible percutaneously [45]. For the transgastric approach, a dual-channel video gastroscope was used, the stomach wall was punctured using a needle-knife, a guidewire was passed into the abdominal cavity, and the access dilated using a controlled radial expansion balloon. The bowel was mobilized medially and the Gerota’s fascia overlying the upper pole was dissected. For the transvaginal approach the gastroscope was introduced through the posterior fornix of the vagina. After gaining intraperitoneal access and complete dissection of the kidney upper pole, the Veress needle was removed and replaced by a 2.4-mm cryoprobe, which was inserted at the same skin puncture site of the Veress needle under direct gastroscopic control. Pneumoperitoneum was maintained by continuous insufflation through the gastroscope. Two freezing cycles were performed and the ice ball formation and advancement were monitored gastroscopically. Four procedures were performed successfully, with no intraoperative complications. Stomach closure was tested watertight, and there were no abdominal or pelvic injuries found at autopsy. Limitations were represented by the lack of suitable instrumentation to use through the gastroscope. A specific NOTES cryoprobe that might be inserted through the gastroscope working channel or alongside the gastroscope needs to be developed to be able to perform a pure NOTES cryoablation by introducing the cryoprobe through the endoscope. Moreover, a NOTES robotic platform coupled with a surgical navigation system will represent a step forward in this field. Cryoimmunotherapy Thinker et al. investigated whether percutaneous cryoablation of lung metastasis from RCC in combination with aerosolized granulocyte-macrophage colony stimulating factor could induce systemic cellular and humoral immune responses in 6 patients [48]. The immune monitoring data showed that cryoimmunotherapy induced tumor-specific cytotoxic T lymphocyte, specific in vitro antitumor antibody responses, and enhanced Th1 cytokine production in 4 of 6 patients. Interestingly, the magnitude of cellular and humoral antitumor response seems to be associated with clinical responses. Hydrodisplacement Safety and effectiveness of a hydrodisplacement technique during the course of percutaneous renal cryoablation was reported by Bodily et al. [49]. The procedure was

attempted 52 times in 50 percutaneous renal tumor cryoablations. Tumors that were located anteriorly or in the lower pole of the kidney were more likely to require hydrodisplacement. The colon required displacement most often. When fluid was infused, the critical structure was displaced in 50 (96%) of 52 attempts, displacing the critical structure from its initial location by a mean distance of 16 mm. Seldinger technique Investigators from the University of California Irvine described their Seldinger technique of percutaneous renal cryoablation, which was used to manage 13 renal masses in 12 adult patients [50]. Under CT-fluoroscopic guidance, an access needle was inserted to abut the surface of the tumor, followed by an Amplatz super-stiff guidewire and a customized coaxial catheter system, which was used as a conduit for needle biopsy, cryoprobe insertion, and FloSeal instillation. According to the authors, this approach may provide a protective barrier against cryogenic damage to neighboring tissues and theoretically minimize the chance of tract seeding.

Conclusions Cryotechnology is rapidly developing and cryosurgery can nowadays offer the advantage of combining a nephronsparing surgery together with a minimally invasive approach. Given appropriate patient selection, kidney cryoablation shows encouraging intermediate term oncologic outcomes. Major recent advances have been made towards more accurate probe positioning, increased energy delivery, and reduced treatment-related morbidity.

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