THE EFFECTS OF INTENTIONAL CRYOABLATION AND RADIO FREQUENCY ABLATION OF RENAL TISSUE INVOLVING THE COLLECTING SYSTEM IN A PORCINE MODEL

0022-5347/05/1734-1368/0 THE JOURNAL OF UROLOGY® Copyright © 2005 by AMERICAN UROLOGICAL ASSOCIATION

Vol. 173, 1368 –1374, April 2005 Printed in U.S.A.

DOI: 10.1097/01.ju.0000147014.69777.06

THE EFFECTS OF INTENTIONAL CRYOABLATION AND RADIO FREQUENCY ABLATION OF RENAL TISSUE INVOLVING THE COLLECTING SYSTEM IN A PORCINE MODEL NICOLETTE K. JANZEN, KENT T. PERRY, KEN-RYU HAN, BLAINE KRISTO, STEVEN RAMAN, JONATHAN W. SAID, ARIE S. BELLDEGRUN* AND PETER G. SCHULAM* , † From the Departments of Urology (NKJ, KTP, K-RH, BK, ASB, PGS), Radiology (SR) and Pathology (JWS), University of California-Los Angeles School of Medicine, Los Angeles, California

ABSTRACT

Purpose: Ablative techniques for the treatment of urological malignancy are gaining acceptance and they are likely to become more widely used in clinical practice. Indications and limitations of the technologies are still evolving. In a porcine model we evaluated the safety and efficacy of cryotherapy and radio frequency ablation (RFA) of cortical and deep renal tissue. Materials and Methods: In 11 swine argon gas based cryoablation or RFA of renal tissue adjacent to the collecting system was performed using a laparoscopic or percutaneous approach. Lesions created in renal units 30 days or 2 hours prior to harvest were termed chronic or acute. Using single or multiple 17 gauge cryoneedles or 3.0 mm cryoprobes and 2 freeze-thaw cycles (10-minute freeze and 5-minute thaw) 13 acute and 10 chronic cryolesions were made. Using a single 16 gauge umbrella-shaped RFA probe and 2 heating cycles to maximum impedance 13 acute and 4 chronic RFA lesions were made. Gross and microscopic tissue analysis was performed to assess lesion size and renal parenchymal, collecting system and arterial effects. Acute cryolesion size estimation by laparoscopic or transcutaneous ultrasound (US) was compared with pathological lesion size. Results: Acute cryolesions on hematoxylin and eosin staining demonstrated uniform coagulative necrosis of renal parenchyma and chronic cryolesions demonstrated uniform necrosis with fibrous scar formation. Interlobar artery (adjacent to renal pyramid) preservation occurred in 7 of 13 acute and 5 of 9 chronic cryolesions. Urothelial architecture was preserved in 8 of 13 acute and 7 of 9 chronic cryolesions. Acute and chronic RFA lesions demonstrated indeterminate necrosis on hematoxylin and eosin staining, although triphenyl tetrazolium chloride staining of gross specimens confirmed necrosis most definitively in renal cortex. Interlobar artery preservation occurred in 6 of 13 acute and 3 of 4 chronic RFA lesions. Urothelial architecture was preserved in 1 of 13 acute and 2 of 4 chronic RFA lesions. Acute cryolesion dimensions measured by laparoscopic US equaled or underestimated lesion size measured grossly in all 6 cases. Lesion dimensions measured by transcutaneous US equaled or underestimated true lesion size in 3 of 6 cases. In 3 of 6 lesions transcutaneous US overestimated true lesion size by 20%, 76% and 260%, respectively. Conclusions: Renal cortical tissue can be effectively destroyed by cryoablation or RFA. However, treatment of deep parenchymal lesions with either modality may result in incomplete ablation. Cryosurgery but not RFA spares the collecting system in an acute setting. However, healing or regrowth of the urothelium may occur with time after RFA. Laparoscopic US is more accurate for cryolesion monitoring than transcutaneous US. KEY WORDS: carcinoma, renal cell; kidney; swine; cryosurgery; catheter ablation

Although ablative techniques of renal surgery are currently experimental, they comprise an evolving treatment modality. Ablative technologies allow minimally invasive and nephron sparing treatment of renal masses. The 2 competing technologies being used in clinical studies are cryoablation and radio frequency ablation (RFA). Each has been applied laparoscopically, percutaneously or in open fashion. Clinically the current indications for renal cryotherapy and RFA are for the treatment of small (less than 3 to 4 cm), exophytic tumors not involving the collecting system and not Submitted for publication April 8, 2004. Study received animal research committee approval. Supported by Oncura. * Financial interest and/or other relationship with Oncura. † Correspondence: Department of Urology, University of CaliforniaLos Angeles, 10833 LeConte Ave., Los Angeles, California 90095 (telephone: 310-825-1172; FAX: 310-206-5343; e-mail: pschulam@ mednet.ucla.edu).

involving the renal hilum. Because many renal tumors encroach on the hilar area or are located adjacent to the pelvicaliceal system, it is important to investigate the safety and efficacy of cryosurgery and RFA of lesions at these locations. In a porcine model we investigated the effects of thermal ablation using cryosurgery or RFA on cortical and deep renal parenchymal tissue, the collecting system and vascular structures in an acute and chronic setting to determine the safety and efficacy of this approach. Additionally, we studied the efficacy of newer generation 17 gauge (1.47 mm) cryoneedles vs standard 3 mm cryoprobes and the accuracy of laparoscopic vs transcutaneous ultrasound for cryolesion monitoring. MATERIALS AND METHODS

Animals and surgery. A total of 11 female farm pigs weighing between 50 and 75 kg were used in this study, which was

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approved by the animal research committee at our institution. Animals were anesthetized using sodium pentobarbital (35 mg/kg) and maintained on ventilation during all procedures. For survival surgeries veterinary staff monitored animals before and after each procedure in accordance with the National Research Council 1996 Guide for the Care and Use of Laboratory Animals. Animals were sacrificed at varying time points using an overdose of pentobarbital (100 mg/kg). Cryosurgical and RFA equipment. Cryolesions were made with a SeedNet cryoablation unit (Oncura, Westbury, New York) using pressured argon gas at 3,300 psi for ice ball formation and pressurized helium gas at 2,200 psi for thawing. Standard 3 mm diameter cryoprobes or 17 gauge (1.47 mm diameter) cryoneedles were used. RFA lesions were made using a generator with 90 W capacity (Radiotherapeutics, Mountain View, California) with a 16 gauge expandable hook LeVeen probe (Boston Scientific, Natick, Massachusetts). In this probe there are 8 expandable hook umbrellashaped tines. Cryosurgery technique. After anesthesia administration each animal was placed in the lateral decubitus position, and prepared and draped in standard surgical fashion. Baseline serum creatinine was determined prior to surgery. Cryoprobes were placed percutaneously with transcutaneous ultrasound (US) or laparoscopic US assistance. For the laparoscopic US assisted approach a 10 mm port was placed in the midline, through which pneumoperitoneum was achieved. Additional working ports were inserted under direct vision. The kidney was exposed using blunt and sharp dissection. An 8 mHz laparoscopic US probe (B-K Medical, Copenhagen, Denmark) was used to visualize the kidney, guide cryoprobe placement and monitor the size of the ice ball formed. For the nonlaparoscopic approach a 4 mHz transcutaneous US probe (Sonosite, Bothwell, Washington) was used to guide probe placement. Cryoprobes were advanced to the edge of an individual calix without puncturing the collecting system. The goal target lesion thereby encompassed tissue of the renal cortex, adjacent interlobular and arcuate vessels, renal medulla and adjacent interlobar vessels, and caliceal urothelium. Two freeze-thaw cycles (10-minute freeze and 5-minute thaw) were used in all cases. US measurement of each lesion was done. After confirmation of adequate hemostasis the animals were recovered and observed in the chronic care facility. Animals that underwent survival surgery were evaluated on postoperative day 7 with renal US and serum creatinine measurement. Lesions were created at 2 experimental time points, that is 30 days prior to sacrifice (chronic lesion) and 2 hours prior to sacrifice (acute lesion). RFA technique. Animals were positioned as described for the cryoablation technique. A 16 gauge LeVeen probe was placed percutaneously under real time transcutaneous US guidance and advanced to the edge of a calix without perforating the collecting system. The tines were expanded fully in a predetermined circular umbrella shape 2 cm in diameter. Lesions were created using 2 heating cycles to maximum impedance. As in pigs treated with cryoablation, RFA lesions were created at 2 experimental time points, namely 30 days prior to sacrifice (chronic lesion) and 2 hours prior to sacrifice (acute lesion). Tissue analysis. Following sacrifice kidneys were harvested and gross lesion size was measured. Following harvest tissues were serially sectioned at 10 mm intervals, fixed in 10% neutral buffered formalin and embedded in paraffin blocks. Histological sections were cut at 5 ␮m and stained with hematoxylin and eosin for microscopic analysis. Additionally, to confirm necrosis gross RFA lesions were stained with triphenyl tetrazolium chloride (TTC), a dye that forms a red stain in the presence of intact dehydrogenase enzyme systems.1 Areas of viable tissue stain red and areas of necrosis lacking dehydrogenase activity fail to stain.

TABLE 1. Intraoperative and postoperative data Cryoablation Probe mm type (No.) Mean ablation time (secs) Mean lesion temperature (C) Mean ice ball max diameter (mm) Mean survival time (days) Mean postop creatinine (mg/dl) Mean pathological acute lesion size max diameter (mm) Complications (No.)

RFA

1.5 (1–5), 3.0 (1–2) 1,200 ⫺54.7 (min)* 26.4

654 68 (max) –

34 1.4 32.1

29 1.4 23.5

Peroneal nerve injury (1), enterotomy repaired laparoscopically (2) * Lowest recordable probe temperature was ⫺75C.

2.0 (1)

None

RESULTS

Table 1 lists intraoperative and postoperative data. In 11 pigs a total of 13 acute cryolesions, 13 acute RFA lesions, 10 chronic cryolesions and 4 chronic RFA lesions were made. All animals survived chronic cryoablation and RFA surgeries without significant morbidity. One animal sustained a peroneal nerve injury that resolved after 24 hours. In 2 animals undergoing laparoscopic assisted cryoablation small, inadvertent enterotomies occurred, which were repaired laparoscopically without postoperative sequelae. US on postoperative day 7 revealed no sonographic evidence of urinoma or hematoma and serum creatinine levels obtained on postoperative day 7 were unchanged from baseline in all 11 animals. Gross findings. Acute cryolesions appeared well circumscribed and hemorrhagic (fig. 1, A). At 1 month cryolesions appeared contracted with a yellow color. Lesions created a divot on the gross surface of the kidney (fig. 1, B). Acute RFA lesions were tan with an irregular, thin hemorrhagic border. Parenchymal tissue appeared cracked with distinctly visible tine tracks on gross examination (fig. 1, C). At 1 month RFA lesions appeared grossly similar to acute lesions. Lesions did not contract and they maintained a tan color with visible tine tracks (fig. 1, D). Renal parenchymal findings. Acute and Chronic Cryoablation Lesions: On hematoxylin and eosin staining acute cryolesions demonstrated uniform coagulative necrosis of cortical and deep renal parenchyma with a 1 to 2 mm wide rim of sublethal injury noted at the lesion periphery (fig. 2, A and B). At 30 days the chronic cryolesion demonstrated complete necrosis within the central portion of the scar. A rim of sublethal injury was similarly noted at the periphery of the lesion with evidence of polymorphonuclear cell invasion and collagen deposition (fig. 2, C). Acute and Chronic RFA Lesions: On hematoxylin and eosin staining acute and chronic RFA lesions demonstrated variable areas of parenchymal cracking and bleeding with evidence of hemorrhagic necrosis immediately adjacent to these areas (fig. 3, A). Large portions of RFA treated tissue demonstrated evidence of early ischemia but not definitive necrosis on hematoxylin and eosin staining (fig. 3, B). However, TTC staining of the gross specimen confirmed tissue necrosis located in the renal cortex in all cases, although in tissue located adjacent to the pelvicaliceal system a red stain was noted, indicating the presence of intact dehydrogenase enzyme systems, which is an indicator of cell viability (fig. 3, C). Interlobar artery findings. Arteries within the lesion or immediately adjacent to ablated tissue were classified as preserved if the endothelial layer remained intact, smooth muscle cell nuclei appeared normal and a fibrin clot within the lumen of the artery was absent (fig. 4, A). Destroyed interlobar arteries demonstrated a loss of endothelium, a

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FIG. 1. Gross appearance of bivalved porcine kidney following cryoablation. Uniform hemorrhagic lesion was noted after 2 hours (A) and contracted scar was noted after 30 days (B). RFA lesions after 2 hours (C) and 30 days (D) demonstrated similar whitish-tan appearance with cracking and visible tine tracks.

luminal fibrin clot and damaged smooth muscle (fig. 4, B) Lesions were labeled indeterminate if interlobar vessels were not present on the specimen. Variable preservation of interlobar arteries located adjacent to the renal medulla was noted in lesions created by cryoablation and by RFA. Table 2 lists interlobar artery findings. Preservation of interlobar arteries occurred in 8 of 13 acute cryolesions, 7 of 13 acute RFA lesions, 5 of 9 chronic cryolesions and 3 of 4 chronic RFA lesions. Destruction of interlobar arteries was seen in 3 of 13 acute cryolesions, 4 of 13 acute RFA lesions, 4 of 9 chronic cryolesions and 1 of 4 chronic RFA lesions. Interlobular artery destruction was not quantified because histological analysis of acute and chronic cryoablation and RFA lesions demonstrated uniform destruction of these smaller vessels located in the renal cortex (fig. 4, C). Collecting system findings. Table 2 also lists collecting system findings. Urothelial architecture was preserved in 8 of 13 acute and 7 of 9 chronic cryolesions. In contrast, urothelial architecture was preserved in 1 of 13 acute RFA lesions and 2 of 4 chronic RFA lesions. Urothelial effects were indeterminate in 4 of 13, 0 of 13, 4 of 13 and 2 of 4 acute cryolesions, chronic cryolesions, acute RFA lesions and chronic RFA lesions, respectively (fig. 5). Comparison of 17 gauge cryoneedles vs 3 mm cryoprobes. The average diameter of the cryolesion formed by 17 gauge cryoneedles vs 3 mm cryoprobes spaced approximately 0.75 cm apart varied with the number of needles or probes used. Table 3 lists these results. Average diameter of the lesions formed with 1, 3 or 5, 17 gauge cryoneedles was 2.0, 2.6 and 3.8 cm, respectively. Average diameter of the lesions formed with 1 or 2, 3 mm cryoprobes was 2.5 and 4.2 cm, respectively. Uniform and complete ablation was observed in all cryolesions regardless of probe type used. Laparoscopic vs transcutaneous US monitoring of cryolesion. Acute cryolesion dimensions measured by laparoscopic US equaled or underestimated the lesion size measured grossly in all 6 cases. Median lesion area measured by laparoscopic US was 6.7 cm2 compared with 7.6 cm2 for pathological lesion. Average lesion area was 18.5% larger than that

FIG. 2. Microphotograph demonstrates coagulative necrosis of renal cortex (A) and medulla (B) after acute cryoablation. Trichrome stain, reduced from ⫻120. Complete necrosis within central portion of scar with rim of sublethal injury was seen after chronic cryoablation (C). H & E, reduced from ⫻80.

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FIG. 3. Microphotograph shows variable areas of parenchymal cracking and bleeding after acute RFA (A). H & E, reduced from ⫻80. Variable necrosis (closed arrow) within central portion of scar was also seen after chronic RFA (B). Open arrow indicates ischemia. H & E, reduced from ⫻120. TTC staining of gross specimen after acute RFA (C) confirmed necrosis in portions of RFA lesion lacking red color.

measured by laparoscopic US. Lesion dimensions measured by transcutaneous US equaled or underestimated true lesion size in 3 of 6 cases. In the remaining 3 of 6 lesions transcutaneous US overestimated true lesion size by 20%, 76% and 260%, respectively. The median lesion area measured by transcutaneous US was 5.1 cm2 compared with 4.2 cm2 for the pathological lesion. DISCUSSION

Ablative techniques in the treatment of urological cancer are gaining acceptance and are likely to become more widely

used in clinical practice. However, a consensus on the applications and limitations of these technologies does not exist. Clinical and experimental data on the use of 17 gauge cryoneedles in renal cryosurgery is lacking. The results of this animal study address several outstanding issues in the application and limitation of ablative techniques in the treatment of renal masses and they may help to establish clinical guidelines. Cryosurgery for small peripheral renal lesions not involving the pelvicaliceal system has shown promising short-term results in several clinical series.2⫺6 Gill et al presented the

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tumors) or percutaneously 1 week prior to nephrectomy (6 tumors).10 On pathological examination 4 of 5 tumors harvested immediately following RFA and 3 of 6 harvested 1 week after RFA demonstrated residual viable tumor. Pathological analysis in these cases was performed with hematoxylin and eosin staining. However, it has been shown that conventional hematoxylin and eosin staining of tissue sections following RFA is not a reliable method for evaluating cell viability. Michaels et al performed RFA of a total of 20 tumors in 15 patients via an open approach immediately before partial nephrectomy.11 Residual tumor was noted in all cases on histological examination using hematoxylin and eosin and 4 of 5 tumors examined with nicotinamide adenine dinucleotide staining demonstrated residual tumor. It has been postulated that these early studies may have resulted in treatment failures due to a heat sink phenomenon caused by the use of less powerful generators. A more powerful generators with a 200 W capacity was evaluated in a more recent series. Matlaga et al performed RFA using a saline cooled probe and a 200 W generator of a total of 10 tumors in 10 patients prior to partial or radical nephrectomy.12 Successful ablation was achieved in 8 of 10 tumors. In 1 treatment failure adequate ablation temperature was not obtained. The second treatment failure was that of an 8 cm tumor. In our study indeterminate necrosis was demonstrated on hematoxylin and eosin staining in acute and chronic RFA lesions. However, complete necrosis within RFA lesions was confirmed using the TTC staining technique, most definitively in the renal cortex. Uniform ablation of interlobular arteries located in the renal cortex provides further evidence of the ablative capacity of RFA in peripheral tissue. In tissue adjacent to the pelvicaliceal system stained with TTC a colored precipitate was noted, indicating the presence of intact dehydrogenase enzyme systems, which is an indicator of cell viability. A high rate of incomplete destruction of the interlobar arteries located in the medulla provided further evidence of incomplete ablation in this area. Our use of an early generation, 90 W generator may have been responsible for this finding. However, several published clinical series have demonstrated successful RFA of cortical and exophytic renal tumors, and less successful ablation of central lesions,13⫺15 consistent with our findings. Collecting system effects have rarely studied. Sung et al reported that intentional cryoablation of the collecting system did not result in urinoma or fistula formation in a chronic porcine model and urothelium appears resistant to damage histologically.16 Our results of urothelial preservation in a large percent of cryolesions are consistent with this report. In contrast to cryoablation, acute RFA demonstrated a high rate of urothelial damage on histological analysis in our study. However, examination of the collecting system in chronic RFA lesions showed an intact urothelium, possibly indicating regeneration or healing with time. In no case did histological damage to the collecting system result in a clinically detectable complication such as fistula or urinoma formation. The evolution of third-generation cryosurgery includes the use of gas driven probes or cryoprobes, in which pressurized

largest series of laparoscopic cryoablation of a total of 34 peripheral renal tumors in 32 patients.3 At a mean followup of 16.2 months no radiographic evidence of local or port site recurrence was demonstrated. Computerized tomography (CT) guided needle biopsy at 3 and 6 months of 23 ablated tumors was negative for viable cancer cells in all cases. Lee et al presented the results of laparoscopic cryoablation of peripheral renal tumors in 20 patients.4 No radiographic evidence of recurrence was demonstrated in all patients, of whom 8 were followed a minimum of 2 years. Shingleton and Sewell reported the results of percutaneous magnetic resonance imaging (MRI) guided cryoablation of 22 lesions in 20 patients.2 At a mean followup of 9.1 months a single patient with an initial 5 cm tumor showed radiographic evidence of persistent tumor following treatment. To our knowledge the efficacy of intentional cryoablation of deep renal tissue adjacent to the collecting system has not been studied. Our study confirms the efficacy of cryosurgery for attaining adequate necrosis of the renal cortex in an acute and chronic model. Complete necrosis of tissue in the cortex as well as the blood supply to this area in the form of interlobular arteries confirms the efficacy of ablation of peripheral masses. However, despite the histological appearance of tissue necrosis in the renal medulla following cryosurgery, incomplete destruction of the interlobar arteries located in the medulla raises concern about the persistence of viable cells in the adjacent area. This finding warrants caution for the treatment of deeper renal tumors. Clinically there appears to be evidence for tumor persistence after cryosurgery of deep lesions. When reviewing MRI guided percutaneous cryosurgery treatment failures, Shingleton found that they occurred only in cases of deeper tumors located adjacent to the pelvicaliceal system (personal communication). RFA for the treatment of renal tumors has been applied with varying success in several clinical studies. Gervais et al performed percutaneous RFA of a total of 9 renal tumors in 8 patients.7 Tumors were located peripherally or centrally with a mean size of 3.3 cm. Tumors demonstrating enhancement on MRI following treatment underwent additional RFA procedures and 24 treatments were performed at 14 sessions. At a mean followup of 10.3 months all 5 exophytic tumors showed no evidence of radiological recurrence. However, 2 of 3 centrally located tumors (4.4 and 5.0 cm, respectively) demonstrated persistent enhancement. Pavlovich et al performed percutaneous RFA using ultrasound or CT guidance of a total of 24 tumors in 21 patients with hereditary renal tumors.8 At least 2 treatments per tumor were performed. At a followup of 2 months 19 of 24 tumors demonstrated no radiographic evidence (CT) of recurrence, although 5 showed enhancement. Lewin et al performed percutaneous RFA with MRI guidance of a total of 10 tumors in 10 patients.9 At a mean followup of 18.5 months no radiographic evidence (MRI) of residual tumor was noted in any patient. Incomplete renal tumor ablation on histological analysis using RFA in experimental protocols has been reported. Rendon et al performed RFA of small renal masses in 10 patients in open fashion immediately prior to partial or radical nephrectomy (5

TABLE 2. Interlobar artery and collecting system preservation No. Preserved (%) Interlobar artery: Acute cryosurgery Chronic cryosurgery Acute RFA Chronic RFA Collecting system: Acute cryosurgery Chronic cryosurgery Acute RFA Chronic RFA

8 5 6 3

(61.5) (55.6) (46.2) (75)

8 (61.5) 7 (77.8) 1 (7.7) 2 (50)

No. Destroyed (%)

No. Indeterminate (%)

Total No.

(23.1) (44.4) (30.7) (25)

2 (15.4) 0 3 (23.1) 0

13 9 13 4

1 (7.7) 2 (22.2) 8 (61.5) 0

4 (30.8) 0 4 (30.7) 2 (50)

13 9 13 4

3 4 4 1

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FIG. 4. Low power microphotograph reveals intact interlobar artery in cryolesion (A). H & E, reduced from ⫻80. Inset demonstrates high power microphotograph (B). H & E, reduced from ⫻120. Destroyed interlobular artery within renal cortex shows fibrin clot and endothelial cell layer loss (C). Trichrome stain, reduced from ⫻120.

gas can be used to freeze (argon gas) and actively thaw (helium gas) the organ. The transition from liquid to gas permits the use of smaller diameter probes, eliminating the need for tract dilation and insertion kits.17 In this study complete tissue ablation was demonstrated using 17 gauge (1.47 mm) cryoneedles or 3 mm cryoprobes. Three mm probes resulted in larger lesion sizes, although similar lesion sizes can be achieved with multiple 17 gauge cryoneedles. An advantage of the 17 gauge cryoneedles over 3 mm probes is that they create less bleeding at the time of placement. Pure percutaneous and laparoscopic assisted approaches to cryoablation are currently used clinically. We found that laparoscopic US more accurately measures renal cryolesion size than transcutaneous US. Alternative approaches to percutaneous probe placement guidance are CT or MRI.2, 18 However, these approaches require collaboration with an interventional radiologist skilled at percutaneous cryoablation, which may not be widely available. Newer generation 3-dimesional US equipment may improve the accuracy of tumor targeting and cryolesion monitoring during transcutaneous US guided percutaneous cryosurgery but it requires further investigation.

FIG. 5. Microphotograph demonstrates intact urothelial layer (closed arrow) after acute (A) and chronic (B) cryoablation adjacent to collecting system (open arrow). H & E, reduced from ⫻80. Following acute RFA urothelial layer showed sloughing with cytoplasmic vacuolization (closed arrow) adjacent to collecting system (open arrow) at low power (C). Trichrome stain, reduced from ⫻80. Inset, high power view (D). Trichrome stain, reduced from ⫻120.

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CRYOABLATION AND RADIO FREQUENCY ABLATION OF RENAL TISSUE TABLE 3. Cryoprobe selection and lesion size

No. 17 gauge cryoneedles: 1 3* 5* No. 3.0 mm cryoprobes: 1 2* * Placed 0.5 to 0.75 cm apart.

No. Lesions

Av Diameter (cm)

1 3 2

2.0 2.6 3.8

3 1

2.5 4.2

CONCLUSIONS

Cortical and exophytic masses can be treated effectively with cryoablation or RFA. Incomplete ablation of larger interlobar vessels in deeper renal tissue raises concern for the possibility of persistent tumor following ablation. Deep parenchymal lesions may result in incomplete ablation with cryosurgery and RFA. Cryosurgery but not RFA appears to spare the collecting system in the setting of acute lesion formation. However, healing or regrowth of the urothelium appears to occur with time in RFA lesioning. Therefore, from a safety standpoint RFA and cryosurgery appear to be equally safe in regard to the collecting system. The 1.5 mm and 3.0 mm cryoprobes are safe and provide uniform ablation of renal tissue, although 1.5 mm cryoprobes may be technically advantageous because they can be safely placed percutaneously without access sheaths. Laparoscopic US is more accurate for cryolesion monitoring than transcutaneous US. The urologist should be aware of the benefits and limitations of technologies such as cryoablation and RFA to ensure appropriate patient selection. Dr. Michael C. Fishbein, Department of Pathology provided TTC stain, Dr. Dorina Gui, Department of Pathology assisted with tissue block preparation and Michelle Moeck, Department of Urology, assisted with graphics. REFERENCES

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5. Bishoff, J. T., Chen, R. B., Lee, B. R., Chan, D. Y., Huso, D., Rodriguez, R. et al: Laparoscopic renal cryoablation: acute and long-term clinical, radiographic, and pathologic effects in an animal model and application in a clinical trial. J Endourol, 13: 233, 1999 6. Gill, I. S., Novick, A. C., Soble, J. J., Sung, G. T., Remer, E. M., Hale, J. et al: Laparoscopic renal cryoablation: initial clinical series. Urology, 52: 543, 1998 7. Gervais, D. A., McGovern, F. J., Wood, B. J., Goldberg, S. N., McDougal, W. S. and Mueller, P. R.: Radio-frequency ablation of renal cell carcinoma: early clinical experience. Radiology, 217: 665, 2000 8. Pavlovich, C. P., Walther, M. M., Choyke, P. L., Pautler, S. E., Chang, R., Linehan, W. R. et al: Percutaneous radio frequency ablation of small renal tumors: initial results. J Urol, 167: 10, 2002 9. Lewin, J. S., Nour, S. G. and Connell, C. F.: Follow up findings of a phase II trial of interactive MR-guided radiofrequency thermal ablation of primary kidney tumors. Presented at Proceedings of 10th Scientific Meeting of the International Society for Magnetic Resonance in Medicine, Honolulu, Hawaii, May 18 – 24, 2002 10. Rendon, R. A., Gertner, M. R., Sherar, M. D., Asch, M. R., Kachura, J. R., Sweet, J. et al: Development of a radio frequency based thermal therapy technique in an in vivo porcine model for the treatment of small renal masses. J Urol, 166: 292, 2001 11. Michaels, M. J., Rhee, H. K., Mourtzinos, A. P., Summerhayes, I. C., Silverman, M. L. and Libertino, J. A.: Incomplete renal tumor destruction using radio frequency interstitial ablation. J Urol, 168: 2406, 2002 12. Matlaga, B. R., Zagoria, R. J., Woodruff, R. D., Torti, F. M. and Hall, M. C.: Phase II trial of radio frequency ablation of renal cancer: evaluation of the kill zone. J Urol, 168: 2401, 2002 13. Farrell, M. A., Charbonneau, W. J., DiMarco, D. S., Chow, G. K., Zincke, H., Callstrom, M. R. et al: Imaging-guided radiofrequency ablation of solid renal tumors. AJR Am J Roentgenol, 180: 1509, 2003 14. Gervais, D. A., McGovern, F. J., Arellano, R. S., McDougal, W. S. and Mueller, P. R.: Renal cell carcinoma: clinical experience and technical success with radio-frequency ablation of 42 tumors. Radiology, 226: 417, 2003 15. Mayo-Smith, W. W., Dupuy, D. E., Parikh, P. M., Pezzullo, J. A. and Cronan, J. J.: Imaging-guided percutaneous radiofrequency ablation of solid renal masses: techniques and outcomes of 38 treatment sessions in 32 consecutive patients. AJR Am J Roentgenol, 180: 1503, 2003 16. Sung, G. T., Gill, I. S., Hsu, T. H. S., Meraney, A. M., Skacel, M., Brainard, J. A. et al: Effect of intentional cryo-injury to the renal collecting system. J Urol, 170: 619, 2003 17. Han, K. R. and Belldegrun, A. S.: Third-generation cryosurgery for primary and recurrent prostate cancer. BJU Int, 93: 14, 2004 18. Harada, J., Dohi, M., Mogami, T., Fukuda, K., Miki, K., Furuta, N. et al: Initial experience of percutaneous renal cryosurgery under the guidance of a horizontal open MRI system. Radiat Med, 19: 291, 2001