- Email: [email protected]
Ultrasound Guided Percutaneous Microwave Ablation for Small Renal Cancer: Initial Experience
Ultrasound Guided Percutaneous Microwave Ablation for Small Renal Cancer: Initial Experience Ping Liang,* Yang Wang, Dakun Zhang, Xiaoling Yu, Yongyan Gao and Xiaoxia Ni From the Department of Ultrasound, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China
Purpose: We evaluated the feasibility, safety and efficacy of ultrasound guided percutaneous microwave ablation for small renal cell cancers. Materials and Methods: A total of 12 patients with a pathologically proven renal cell cancer 1.3 to 3.8 cm in diameter were treated with microwave ablation. A cooled shaft needle antenna was percutaneously inserted into the tumor under ultrasound guidance. One antenna was used for tumors 2 cm or smaller and antennae were used for tumors larger than 2 cm. One thermocouple was placed about 0.5 cm away from the tumor to monitor temperature in real time during ablation. Microwaves were emitted at 50 W for 500 seconds and prolonged as necessary to attain temperatures sufficient to ensure tumor kill. Immediate treatment efficacy was assessed by contrast enhanced ultrasound 1 day after ablation. Short-term efficacy was assessed by contrast enhanced computerized tomography and/or contrast enhanced ultrasound at 1, 3 and 6 months, and every 6 months thereafter. Results: All tumors were completely ablated at a single session and no complications occurred. No residual tumor or recurrence was observed at a median followup of 11 months (range 4 to 20). The ablation zone was well defined on contrast enhanced imaging and it gradually shrank with time. Conclusions: Ultrasound guided percutaneous microwave ablation appears to be a safe and effective technique for small renal cell cancer in select patients. Key Words: kidney; carcinoma, renal cell; ultrasonography; microwaves
he incidence of RCC continues to increase. In the United States alone up to 35,000 new cases of RCC occur annually.1 Fortunately due to the widespread use of cross-sectional imaging modalities such as ultrasound and CT many RCCs are detected at an early stage, so that they are usually small and localized, and tend to have a favorable prognosis.2 Radical nephrectomy used to be the only curative treatment for early stage RCC.3 More recently nephron sparing surgery or partial nephrectomy has gained popularity and been adopted by an increasing number of urologists in select patients.4,5 Although it is less invasive than radical nephrectomy, partial nephrectomy is technically challenging and it may have serious complications, such as excessive blood loss and urinary fistula. The reported complication rate can be as high as 30.1%.6 Percutaneous image guided thermal ablation is a promising technique for early stage RCC compared with surgery, which can attain satisfactory tumor control with significantly lower complication rates.7–11 Also, due to its minimal invasiveness it can also be used in patients who are poor surgical candidates. Currently almost all reports of thermal ablation for RCC are about cryoablation or RF. MW is a thermal ablation technique that results in long-term survival comparable to that of surgery for hepatocellular carcinoma.12–14 However,
to our knowledge it has not been used for RCC as a curative approach. Thus, we evaluated the efficacy and safety of ultrasound guided percutaneous MW ablation for RCC.
T
MATERIALS AND METHODS Patients From April 2006 to August 2007, 12 consecutive patients with pathologically proven, unilateral small localized RCC received percutaneous MW ablation as the only treatment at our department. All patients were treated as inpatients. Institutional review board approval was obtained and all patients provided informed consent at enrollment. Inclusion criteria were 1) a peripherally located single lesion 4 cm or smaller, 2) no tumor invasion to the renal pelvis/calix, 3) tumors not abutting the bowel or ureter, 4) absent renal vein tumor thrombus or extrarenal metastasis, 5) an appropriate puncture route noted on ultrasound and 6) a general patient condition permitting MW ablation, as assessed by a consensus of 4 interventional radiologists (LP, YW, DKZ and XLY). There were 7 men and 5 women 35 to 80 years old (mean age 57). Of the patients 11 had normal serum urea nitrogen (no more than 7.4 mmol/l) and creatinine (no more than 110 mol/l). One patient had impaired renal function requiring no dialysis with serum urea nitrogen 10.7 mmol/l and serum creatinine 273 mol/l. All patients had no absolute contraindications to nephrectomy. They elected MW ablation instead of radical or partial nephrectomy for fear of surgical risks, postoperative pain or cosmetic reasons. Tumor size was 1.3 to 3.8 cm (mean 2.5). Ten tumors were exophytic and 2 were intraparenchymal (see table).
Submitted for publication December 23, 2007. Study received institutional review board approval. * Correspondence: Department of Ultrasound, Chinese People’s Liberation Army General Hospital, 28 Fuxing Rd., Beijing, 100853, People’s Republic of China (telephone: 86-10-66939530; FAX: 86-1088210006, e-mail: [email protected]).
0022-5347/08/1803-0844/0 THE JOURNAL OF UROLOGY® Copyright © 2008 by AMERICAN UROLOGICAL ASSOCIATION
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Vol. 180, 844-848, September 2008 Printed in U.S.A. DOI:10.1016/j.juro.2008.05.012
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Patient and tumor characteristics Pt No.—Age—Sex 1—59 2—39 3—80 4—74 5—76 6—78 7—37 8—43 9—35 10—55 11—53 12—53
—M —F —M* —M —M —M —F —F —F —M† —F —M
Tumor Tumor Size (cm)
Type
Site
MW Ablation Time (secs)
Followup (mos)
Followup Contrast Imaging
2.7 1.3 1.9 3.6 2.3 3.3 1.8 1.5 2.2 3.8 2.5 3.1
Exophytic Intraparenchymal Exophytic Exophytic Exophytic Exophytic Exophytic Intraparenchymal Exophytic Exophytic Exophytic Exophytic
Mid RK Upper LK pole Mid RK Upper RK pole Mid LK Upper RK pole Mid RK Mid LK Mid RK Upper RK pole Lower RK pole Upper RK pole
500 500 600 600 500 500 600 500 500 700 500 500
20 19 4 16 15 11 10 9 8 8 6 4
CT CT CT CT CT CT CT CT CT US CT CT
There were no recurrences. * Patient died 4 months after MW ablation of acute bleeding from a peptic ulcer. † Patient had impaired renal function and refused contrast enhanced CT for followup, so that contrast enhanced ultrasound was performed instead, and serum urea nitrogen and creatinine were 10.7 mmol/l and 273 mol/l, respectively, before MW ablation, which did not change significantly after treatment.
Equipment A KY2000 MW ablation system (Kangyou Medical Instruments, Nanjing, People’s Republic of China) consists of a MW generator, a flexible coaxial cable and a cooled shaft antenna. The generator is capable of producing 1 to 100 W of power at 2,450 MHz, which can drive up to 2 antennae simultaneously. The cooled shaft antenna has a 15 gauge shaft coated with polytetrafluoroethylene to prevent adhesion, which can be easily seen on ultrasound. The antenna was designed to minimize power feedback and provide optimal energy deposition into tissue. Inside the antenna shaft there are dual channels through which distilled water is circulated by a peristaltic pump, continuously cooling the shaft to prevent shaft overheating (fig. 1). The MW machine is also equipped with a thermal monitoring system that can measure temperature in real time during ablation. Ablation Procedures Before treatment all patients underwent contrast enhanced CT and ultrasound, and an appropriate puncture route was chosen on ultrasound. After local anesthesia with 1% lidocaine was administered ultrasound guided biopsy was performed by an automatic biopsy gun with an 18 gauge cutting needle. Three specimens were obtained. The antenna was then percutaneously inserted into the tumor and placed at designated sites under ultrasound guidance. For tumors less than 2 cm 1 antenna was inserted in the center of the tumor and for tumors 2 cm or greater 2 antennae were inserted inside the tumor with an interantenna distance of no more than 1.8 cm. The 2 antennae were used simultaneously during MW ablation to achieve a larger ablation zone. The rationale is based on our previous experience with MW ablation for liver cancer using the cooled shaft antenna that applying 1 antenna could yield an ellipsoidal ablation zone sufficient to induce complete necrosis of tumors less than 2 cm, while the simultaneous application of 2 antennae could yield a confluent ablation zone for complete coverage of tumors less than 4 cm when properly positioned. A 20 gauge thermocouple was inserted in the renal parenchyma about 0.5 cm away from the tumor for real-time temperature monitoring during MW ablation. All insertions were performed by 1 of 2 experienced radiologists (LP and XLY), who had cooperated for more than 10 years in MW ablation for hepatocellular carcinoma.
After all insertions intravenous anesthesia was administered by a combination of propofol and ketamine via the peripheral vein. An power output of 50 W for 500 seconds was routinely used during MW ablation. If the heat generated hyperechoic water vapor did not completely encompass
FIG. 1. Antenna used for MW ablation showing MW antenna needle (left), slit emitting segment mounted near needle tip (arrowhead) and 2 channels (arrowheads) for water circulation (right).
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the entire tumor and measured temperature did not attain 60C or remain above 54C for at least 3 minutes, prolonged MW emission was applied at an increment of 100 seconds until the desired temperature was achieved. When withdrawing the antenna, the needle track was coagulated to prevent tumor cell seeding. Postprocedual Observation and Imaging Followup After MW ablation patients were closely monitored for possible complications, such as gross hematuria, urinoma and skin burn. Side effects such as fever, pleural effusion and pain were also documented. Urinalysis was performed immediately after treatment and once daily for 3 days. Serum urea nitrogen and creatinine were tested 1 and 3 days after treatment. All patients underwent contrast enhanced ultrasound 1 day after MW ablation to assess treatment efficacy. If residual tumor was found, a further session was planned or patients entered the followup protocol, which consisted of contrast enhanced CT and/or contrast enhanced ultrasound 1, 3, 6 months after MW ablation, and every 6 months thereafter. RESULTS All tumors were clear cell carcinoma on pathological examination. MW ablation was well tolerated by all patients. Desired temperatures were attained in no more than 700 seconds (range 500 to 700). Slight perirenal hemorrhage was noted in 2 patients when inserting the antennae, which was controlled shortly after MW emission. No major complications occurred during or immediately after MW ablation. After treatment 8 patients experienced mild pain at the puncture site, requiring no analgesic medication. Pain was grade 1 pain according to standardization of terms and reporting criteria for image guided tumor ablation.15 Tran-
sient microscopic hematuria was detected in all patients immediately after treatment, which disappeared 2 to 3 days after treatment. Serum urea nitrogen and creatinine did not change significantly after MW ablation in all patients. During followup the 11 patients without pre-ablation renal insufficiency had normal renal function. Renal function in the patient with pre-ablation renal insufficiency did not worsen enough to necessitate dialysis. Because contrast enhanced ultrasound showed no residual tumor in all patients 1 day after treatment, patients were discharged home 4 days after treatment and followed regularly according to the protocol. During a median followup of 11 months (range 4 to 20) 1 patient died of acute bleeding from a peptic ulcer 4 months after MW ablation. The remaining patients had no recurrence on imaging. The ablation zone was well defined on contrast enhanced CT and contrast enhanced ultrasound, and it gradually shrank with time (figs. 2 and 3). DISCUSSION Management for RCC underwent a dramatic evolution in the last decade, favoring more conservative treatment for clinically localized renal tumors. Of the current treatment options image guided thermal ablation is the least invasive, which can minimize surgical mortality and morbidity, and obviate the need for any parenchymal resection in select patients. By far RF is the most popular thermal ablation technique for small RCC with short-term and intermediate term results comparable to those of surgical resection.7–9 MW is a thermal ablation technique that has been widely used in China for hepatocellular carcinoma with a 5-year survival rate comparable to that of hepatectomy for small hepatic cancers.13,14 Compared with RF, MW may offer
FIG. 2. Contrast CT demonstrates incidentally detected small renal cancer in 59-year-old man treated with MW ablation. A, tumor enhancement before MW ablation. B to D, no ablation zone enhancement 1 month (B), 3 months (C) and 1 year (D) after treatment.
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FIG. 3. Ultrasound shows small renal cancer treated with MW ablation in 55-year-old man with impaired renal function. Patient refused contrast enhanced CT due to concerns about contrast agent renal toxicity. A, tumor (arrow) was well defined and hypoechoic before MW ablation. B, tumor (arrow) showed early washout compared with renal parenchyma with contrast enhancement before MW ablation. C, ablation zone (arrow) was well defined 6 months after treatment. D, using contrast enhancement 6 months after treatment ablation zone was larger than on conventional ultrasound.
some potential advantages.16 MW has a much broader zone of active heating and its transmission in living tissue is not limited by desiccation and charring. Therefore, intratumor temperatures can be driven consistently high, which may contribute to a larger ablation zone, less treatment time and more complete tumor kill. MW is also less affected by the perfusion mediated heat sink effect, which may be helpful for treating tumors with a rich blood supply.17 In addition, multiple antennae can be used simultaneously to ablate larger tumors.12,14 Despite these potential advantages the primitive MW antenna is plagued by high power feedback and energy deposition is hampered, which results in a limited ablation diameter necessitating multiple overlapping ablations even for a small hepatic tumor.18 Therefore, it is only used as an adjuvant technique to minimize bleeding in partial nephrectomy.19,20 In recent years there have been tremendous advances in MW antenna design and current antennae can yield significantly larger ablation diameters, sufficient to ablate hepatic tumors 4 cm or smaller.13,14 Therefore, percutaneous MW ablation may be clinically feasible for small localized RCCs. Clark et al performed a phase I study to ablate RCCs intraoperatively before nephrectomy using an improved antenna.21 Results showed that MW can safely and rapidly generate large ablative RCCs and ablation size was comparable to that of RF. Based on our previous experience with MW ablation for hepatocellular carcinoma to our knowledge we performed the first study of nonexcised percutaneous MW ablation for RCC. Treatment efficacy was encouraging with complete tumor necrosis achieved at a single session of no more than 700 seconds in all lesions and no tumor recurrence was noted during followup. Results suggest that, like other im-
age guided thermal ablation techniques, MW ablation is also feasible for small localized RCCs. The high ablation rate may be attributable to 3 reasons. 1) The cooled shaft antenna used in this study is capable of generating a large enough ablation zone to encompass the entire tumor. 2) There were relatively strict inclusion criteria, all lesions were less than 4 cm and they were confined by pseudocapsules, which facilitated heat deposition during MW ablation. 3) Real-time peritumor temperature served as an indicator for predicting reliable safety margins. No complications were observed in this study, perhaps in part due to the exclusion of tumors adjacent to the bowel and ureter. Selecting an appropriate puncture route also helped minimize complications. Because MW ablation yielded effective tumor kill in these patients without causing complications, it may become a safe and effective technique for small RCCs at favorable locations. Although this was not a randomized, controlled study of traditional surgical techniques, the low complication rate, minimal side effects, speedy recovery and lower costs strongly favor MW ablation as a curative approach for select small RCCs. This study has some limitations. 1) Inclusion criteria were relatively strict, tumor size was limited to 4 cm or smaller and tumors near the hilum or adjacent to important structures such as the bowel or ureter were excluded. Further studies are needed to include larger RCCs and evaluate the possibility of treating tumors at unfavorable locations. 2) Only 12 patients were included in this study. More patients should be recruited and a prospective, randomized study with surgery should be done to better assess treatment safety and efficacy. 3) Followup is relatively short and we are not certain of the long-term results.
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CONCLUSIONS In this pilot study with a short followup ultrasound guided percutaneous MW ablation appeared to be safe and effective for inducing complete necrosis of select small RCCs. Greater experience with this technique should be required before its widespread clinical application.
Abbreviations and Acronyms CT LK MW RCC RF RK
⫽ ⫽ ⫽ ⫽ ⫽ ⫽
computerized tomography left kidney microwave renal cell carcinoma radio frequency right kidney
16.
17.
18.
19.
20.
21.
REFERENCES 1. 2. 3. 4. 5.
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7.
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11.
12.
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15.
Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E et al: Cancer statistics, 2004. CA Cancer J Clin 2004; 54: 8. Zagoria RJ: Imaging of small renal masses: a medical success story. AJR Am J Roentgenol 2000; 175: 945. Robson CJ: Radical nephrectomy for renal cell carcinoma. J Urol 1963; 89: 37. Licht MR and Novick AC: Nephron sparing surgery for renal cell carcinoma. J Urol 1993; 149: 1. Duque JL, Loughlin KR, O’Leary MP, Kumar S and Richie JP: Partial nephrectomy: alternative treatment for selected patients with renal cell carcinoma. Urology 1998; 52: 584. Campbell SC, Novic AC, Steem SB, Klein E and Licht M: Complications of nephron sparing surgery for renal tumors. J Urol 1994; 151: 1177. Gervais DA, McGovern FJ, Wood BJ, Goldberg SN, McDougal WS and Mueller PR: Radio-frequency ablation of renal cell carcinoma: early clinical experience. Radiology 2000; 217: 665. Ogan K, Jacomides L, Dolmatch BL, Rivera FJ, Dellaria MF, Josephs SC et al: Percutaneous radiofrequency ablation of renal tumors: technique, limitations, and morbidity. Urology 2002; 60: 954. Park S, Anderson JK, Matsumoto ED, Lotan Y, Josephs S and Cadeddu JA: Radiofrequency ablation of renal tumors: intermediate-term results. J Endourol 2006; 20: 569. Atwell TD, Farrell MA, Callstrom MR, Charboneau JW, Leibovich BC, Patterson DE et al: Percutaneous cryoablation of 40 solid renal tumors with US guidance and CT monitoring: initial experience. Radiology 2007; 243: 276. Permpongkosol S, Link RE, Kavoussi LR and Solomon SB: Percutaneous computerized tomography guided cryoablation for localized renal cell carcinoma: factors influencing success. J Urol 2006; 176: 1963. Dong BW, Liang P, Yu XL, Zeng XQ, Wang PJ, Su L et al: Sonographically guided microwave coagulation treatment of liver cancer: an experimental and clinical study. AJR Am J Roentgenol 1998; 171: 449. Liang P, Dong BW, Yu XL, Yu DJ, Wang Y, Feng L et al: Prognostic factors for survival in patients with hepatocellular carcinoma after percutaneous microwave ablation. Radiology 2005; 235: 299. Kuang M, Lu MD, Xie XY, Xu HX, Mo LQ, Liu GJ et al: Liver cancer: increased microwave delivery to ablation zone with cooled-shaft antenna— experimental and clinical studies. Radiology 2007; 242: 914. Goldberg SN, Charboneau JW, Dodd GD 3rd, Dupuy DE, Gervais DA, Gillams AR et al: Image-guided tumor ablation: proposal for standardization of terms and reporting criteria. Radiology 2003; 228: 335.
Simon CJ, Dupuy DE and Mayo-Smith WW: Microwave ablation: principles and applications. RadioGraphics, suppl., 2005; 25: S69. Wright AS, Sampson LA, Warner TF, Mahvi DM and Lee FT Jr: Radiofrequency versus microwave ablation in a hepatic porcine model. Radiology 2005; 236: 132. Seki T, Wakabayashi M, Nakagawa T, Itho T, Shiro T, Kunieda K et al: Ultrasonically guided percutaneous microwave coagulation therapy for small hepatocellular carcinoma. Cancer 1994; 74: 817. Naito S, Nakashima M, Kimoto Y, Nakamura M, Kotoh S, Tanaka M et al: Application of microwave tissue coagulator in partial nephrectomy for renal cell carcinoma. J Urol 1998; 159: 960. Yoshimura K, Okubo K, Ichioka K, Terada N, Matsuta Y and Arai Y: Laparoscopic partial nephrectomy with a microwave tissue coagulator for small renal tumor. J Urol 2001; 165: 1893. Clark PE, Woodruff RD, Zagoria RJ and Hall MC: Microwave ablation of renal parenchymal tumors before nephrectomy: phase I study. AJR Am J Roentgenol 2007; 188: 1212.
EDITORIAL COMMENT Nephron sparing approaches for renal masses are becoming increasingly used by urologists. Partial nephrectomy (open or laparoscopic) can be performed with low morbidity and it remains the current gold standard treatment for appropriately selected renal masses.1 Other management options for renal masses include active surveillance or minimally invasive therapies that freeze or cook tumors via cryoablation or RF ablation.2 The current study is rather small with 12 patients and it presents pilot data on the feasibility of ultrasound guided percutaneous MW ablation for small renal tumors. It should also be noted that this is a short-term study with a median followup of less than 1 year and the manner in which tumor recurrence was assessed (via CT or ultrasound) may not be entirely accurate. A better understanding of the efficacy of any new technology for treating renal masses may be gained by further evaluation under an ablate and resect type of protocol to determine whether viable tumor is still present after the initial intervention. Furthermore, uncertainty regarding the ablative zone of MW therapy is not well characterized. As our understanding of the natural history of small renal masses continues to evolve, we are beginning to realize that many renal masses that are treated today with surgery may in the future be observed or treated with ablative therapies. Therefore, we must meet the current challenge of properly evaluating the efficacy of new technologies for cancer treatment before we can safely apply these treatments to widespread clinical use. Mark L. Gonzalgo Department of Urology The James Buchanan Brady Urological Institute The Johns Hopkins Hospital Baltimore, Maryland 1.
2.
Gill IS, Kavoussi LR, Lane BR, Blute ML, Babineau D, Colombo JR et al: Comparison of 1,800 laparoscopic and open partial nephrectomies for single renal tumors. J Urol 2007; 178: 41. Kunkle DA, Egleston BL and Uzzo RG: Excise, ablate or observe: the small renal mass dilemma—a meta-analysis and review. J Urol 2008; 179: 1227.
Purpose: We evaluated the feasibility, safety and efficacy of ultrasound guided percutaneous microwave ablation for small renal cell cancers. Materials and Methods: A total of 12 patients with a pathologically proven renal cell cancer 1.3 to 3.8 cm in diameter were treated with microwave ablation. A cooled shaft needle antenna was percutaneously inserted into the tumor under ultrasound guidance. One antenna was used for tumors 2 cm or smaller and antennae were used for tumors larger than 2 cm. One thermocouple was placed about 0.5 cm away from the tumor to monitor temperature in real time during ablation. Microwaves were emitted at 50 W for 500 seconds and prolonged as necessary to attain temperatures sufficient to ensure tumor kill. Immediate treatment efficacy was assessed by contrast enhanced ultrasound 1 day after ablation. Short-term efficacy was assessed by contrast enhanced computerized tomography and/or contrast enhanced ultrasound at 1, 3 and 6 months, and every 6 months thereafter. Results: All tumors were completely ablated at a single session and no complications occurred. No residual tumor or recurrence was observed at a median followup of 11 months (range 4 to 20). The ablation zone was well defined on contrast enhanced imaging and it gradually shrank with time. Conclusions: Ultrasound guided percutaneous microwave ablation appears to be a safe and effective technique for small renal cell cancer in select patients. Key Words: kidney; carcinoma, renal cell; ultrasonography; microwaves
he incidence of RCC continues to increase. In the United States alone up to 35,000 new cases of RCC occur annually.1 Fortunately due to the widespread use of cross-sectional imaging modalities such as ultrasound and CT many RCCs are detected at an early stage, so that they are usually small and localized, and tend to have a favorable prognosis.2 Radical nephrectomy used to be the only curative treatment for early stage RCC.3 More recently nephron sparing surgery or partial nephrectomy has gained popularity and been adopted by an increasing number of urologists in select patients.4,5 Although it is less invasive than radical nephrectomy, partial nephrectomy is technically challenging and it may have serious complications, such as excessive blood loss and urinary fistula. The reported complication rate can be as high as 30.1%.6 Percutaneous image guided thermal ablation is a promising technique for early stage RCC compared with surgery, which can attain satisfactory tumor control with significantly lower complication rates.7–11 Also, due to its minimal invasiveness it can also be used in patients who are poor surgical candidates. Currently almost all reports of thermal ablation for RCC are about cryoablation or RF. MW is a thermal ablation technique that results in long-term survival comparable to that of surgery for hepatocellular carcinoma.12–14 However,
to our knowledge it has not been used for RCC as a curative approach. Thus, we evaluated the efficacy and safety of ultrasound guided percutaneous MW ablation for RCC.
T
MATERIALS AND METHODS Patients From April 2006 to August 2007, 12 consecutive patients with pathologically proven, unilateral small localized RCC received percutaneous MW ablation as the only treatment at our department. All patients were treated as inpatients. Institutional review board approval was obtained and all patients provided informed consent at enrollment. Inclusion criteria were 1) a peripherally located single lesion 4 cm or smaller, 2) no tumor invasion to the renal pelvis/calix, 3) tumors not abutting the bowel or ureter, 4) absent renal vein tumor thrombus or extrarenal metastasis, 5) an appropriate puncture route noted on ultrasound and 6) a general patient condition permitting MW ablation, as assessed by a consensus of 4 interventional radiologists (LP, YW, DKZ and XLY). There were 7 men and 5 women 35 to 80 years old (mean age 57). Of the patients 11 had normal serum urea nitrogen (no more than 7.4 mmol/l) and creatinine (no more than 110 mol/l). One patient had impaired renal function requiring no dialysis with serum urea nitrogen 10.7 mmol/l and serum creatinine 273 mol/l. All patients had no absolute contraindications to nephrectomy. They elected MW ablation instead of radical or partial nephrectomy for fear of surgical risks, postoperative pain or cosmetic reasons. Tumor size was 1.3 to 3.8 cm (mean 2.5). Ten tumors were exophytic and 2 were intraparenchymal (see table).
Submitted for publication December 23, 2007. Study received institutional review board approval. * Correspondence: Department of Ultrasound, Chinese People’s Liberation Army General Hospital, 28 Fuxing Rd., Beijing, 100853, People’s Republic of China (telephone: 86-10-66939530; FAX: 86-1088210006, e-mail: [email protected]).
0022-5347/08/1803-0844/0 THE JOURNAL OF UROLOGY® Copyright © 2008 by AMERICAN UROLOGICAL ASSOCIATION
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Vol. 180, 844-848, September 2008 Printed in U.S.A. DOI:10.1016/j.juro.2008.05.012
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Patient and tumor characteristics Pt No.—Age—Sex 1—59 2—39 3—80 4—74 5—76 6—78 7—37 8—43 9—35 10—55 11—53 12—53
—M —F —M* —M —M —M —F —F —F —M† —F —M
Tumor Tumor Size (cm)
Type
Site
MW Ablation Time (secs)
Followup (mos)
Followup Contrast Imaging
2.7 1.3 1.9 3.6 2.3 3.3 1.8 1.5 2.2 3.8 2.5 3.1
Exophytic Intraparenchymal Exophytic Exophytic Exophytic Exophytic Exophytic Intraparenchymal Exophytic Exophytic Exophytic Exophytic
Mid RK Upper LK pole Mid RK Upper RK pole Mid LK Upper RK pole Mid RK Mid LK Mid RK Upper RK pole Lower RK pole Upper RK pole
500 500 600 600 500 500 600 500 500 700 500 500
20 19 4 16 15 11 10 9 8 8 6 4
CT CT CT CT CT CT CT CT CT US CT CT
There were no recurrences. * Patient died 4 months after MW ablation of acute bleeding from a peptic ulcer. † Patient had impaired renal function and refused contrast enhanced CT for followup, so that contrast enhanced ultrasound was performed instead, and serum urea nitrogen and creatinine were 10.7 mmol/l and 273 mol/l, respectively, before MW ablation, which did not change significantly after treatment.
Equipment A KY2000 MW ablation system (Kangyou Medical Instruments, Nanjing, People’s Republic of China) consists of a MW generator, a flexible coaxial cable and a cooled shaft antenna. The generator is capable of producing 1 to 100 W of power at 2,450 MHz, which can drive up to 2 antennae simultaneously. The cooled shaft antenna has a 15 gauge shaft coated with polytetrafluoroethylene to prevent adhesion, which can be easily seen on ultrasound. The antenna was designed to minimize power feedback and provide optimal energy deposition into tissue. Inside the antenna shaft there are dual channels through which distilled water is circulated by a peristaltic pump, continuously cooling the shaft to prevent shaft overheating (fig. 1). The MW machine is also equipped with a thermal monitoring system that can measure temperature in real time during ablation. Ablation Procedures Before treatment all patients underwent contrast enhanced CT and ultrasound, and an appropriate puncture route was chosen on ultrasound. After local anesthesia with 1% lidocaine was administered ultrasound guided biopsy was performed by an automatic biopsy gun with an 18 gauge cutting needle. Three specimens were obtained. The antenna was then percutaneously inserted into the tumor and placed at designated sites under ultrasound guidance. For tumors less than 2 cm 1 antenna was inserted in the center of the tumor and for tumors 2 cm or greater 2 antennae were inserted inside the tumor with an interantenna distance of no more than 1.8 cm. The 2 antennae were used simultaneously during MW ablation to achieve a larger ablation zone. The rationale is based on our previous experience with MW ablation for liver cancer using the cooled shaft antenna that applying 1 antenna could yield an ellipsoidal ablation zone sufficient to induce complete necrosis of tumors less than 2 cm, while the simultaneous application of 2 antennae could yield a confluent ablation zone for complete coverage of tumors less than 4 cm when properly positioned. A 20 gauge thermocouple was inserted in the renal parenchyma about 0.5 cm away from the tumor for real-time temperature monitoring during MW ablation. All insertions were performed by 1 of 2 experienced radiologists (LP and XLY), who had cooperated for more than 10 years in MW ablation for hepatocellular carcinoma.
After all insertions intravenous anesthesia was administered by a combination of propofol and ketamine via the peripheral vein. An power output of 50 W for 500 seconds was routinely used during MW ablation. If the heat generated hyperechoic water vapor did not completely encompass
FIG. 1. Antenna used for MW ablation showing MW antenna needle (left), slit emitting segment mounted near needle tip (arrowhead) and 2 channels (arrowheads) for water circulation (right).
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the entire tumor and measured temperature did not attain 60C or remain above 54C for at least 3 minutes, prolonged MW emission was applied at an increment of 100 seconds until the desired temperature was achieved. When withdrawing the antenna, the needle track was coagulated to prevent tumor cell seeding. Postprocedual Observation and Imaging Followup After MW ablation patients were closely monitored for possible complications, such as gross hematuria, urinoma and skin burn. Side effects such as fever, pleural effusion and pain were also documented. Urinalysis was performed immediately after treatment and once daily for 3 days. Serum urea nitrogen and creatinine were tested 1 and 3 days after treatment. All patients underwent contrast enhanced ultrasound 1 day after MW ablation to assess treatment efficacy. If residual tumor was found, a further session was planned or patients entered the followup protocol, which consisted of contrast enhanced CT and/or contrast enhanced ultrasound 1, 3, 6 months after MW ablation, and every 6 months thereafter. RESULTS All tumors were clear cell carcinoma on pathological examination. MW ablation was well tolerated by all patients. Desired temperatures were attained in no more than 700 seconds (range 500 to 700). Slight perirenal hemorrhage was noted in 2 patients when inserting the antennae, which was controlled shortly after MW emission. No major complications occurred during or immediately after MW ablation. After treatment 8 patients experienced mild pain at the puncture site, requiring no analgesic medication. Pain was grade 1 pain according to standardization of terms and reporting criteria for image guided tumor ablation.15 Tran-
sient microscopic hematuria was detected in all patients immediately after treatment, which disappeared 2 to 3 days after treatment. Serum urea nitrogen and creatinine did not change significantly after MW ablation in all patients. During followup the 11 patients without pre-ablation renal insufficiency had normal renal function. Renal function in the patient with pre-ablation renal insufficiency did not worsen enough to necessitate dialysis. Because contrast enhanced ultrasound showed no residual tumor in all patients 1 day after treatment, patients were discharged home 4 days after treatment and followed regularly according to the protocol. During a median followup of 11 months (range 4 to 20) 1 patient died of acute bleeding from a peptic ulcer 4 months after MW ablation. The remaining patients had no recurrence on imaging. The ablation zone was well defined on contrast enhanced CT and contrast enhanced ultrasound, and it gradually shrank with time (figs. 2 and 3). DISCUSSION Management for RCC underwent a dramatic evolution in the last decade, favoring more conservative treatment for clinically localized renal tumors. Of the current treatment options image guided thermal ablation is the least invasive, which can minimize surgical mortality and morbidity, and obviate the need for any parenchymal resection in select patients. By far RF is the most popular thermal ablation technique for small RCC with short-term and intermediate term results comparable to those of surgical resection.7–9 MW is a thermal ablation technique that has been widely used in China for hepatocellular carcinoma with a 5-year survival rate comparable to that of hepatectomy for small hepatic cancers.13,14 Compared with RF, MW may offer
FIG. 2. Contrast CT demonstrates incidentally detected small renal cancer in 59-year-old man treated with MW ablation. A, tumor enhancement before MW ablation. B to D, no ablation zone enhancement 1 month (B), 3 months (C) and 1 year (D) after treatment.
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FIG. 3. Ultrasound shows small renal cancer treated with MW ablation in 55-year-old man with impaired renal function. Patient refused contrast enhanced CT due to concerns about contrast agent renal toxicity. A, tumor (arrow) was well defined and hypoechoic before MW ablation. B, tumor (arrow) showed early washout compared with renal parenchyma with contrast enhancement before MW ablation. C, ablation zone (arrow) was well defined 6 months after treatment. D, using contrast enhancement 6 months after treatment ablation zone was larger than on conventional ultrasound.
some potential advantages.16 MW has a much broader zone of active heating and its transmission in living tissue is not limited by desiccation and charring. Therefore, intratumor temperatures can be driven consistently high, which may contribute to a larger ablation zone, less treatment time and more complete tumor kill. MW is also less affected by the perfusion mediated heat sink effect, which may be helpful for treating tumors with a rich blood supply.17 In addition, multiple antennae can be used simultaneously to ablate larger tumors.12,14 Despite these potential advantages the primitive MW antenna is plagued by high power feedback and energy deposition is hampered, which results in a limited ablation diameter necessitating multiple overlapping ablations even for a small hepatic tumor.18 Therefore, it is only used as an adjuvant technique to minimize bleeding in partial nephrectomy.19,20 In recent years there have been tremendous advances in MW antenna design and current antennae can yield significantly larger ablation diameters, sufficient to ablate hepatic tumors 4 cm or smaller.13,14 Therefore, percutaneous MW ablation may be clinically feasible for small localized RCCs. Clark et al performed a phase I study to ablate RCCs intraoperatively before nephrectomy using an improved antenna.21 Results showed that MW can safely and rapidly generate large ablative RCCs and ablation size was comparable to that of RF. Based on our previous experience with MW ablation for hepatocellular carcinoma to our knowledge we performed the first study of nonexcised percutaneous MW ablation for RCC. Treatment efficacy was encouraging with complete tumor necrosis achieved at a single session of no more than 700 seconds in all lesions and no tumor recurrence was noted during followup. Results suggest that, like other im-
age guided thermal ablation techniques, MW ablation is also feasible for small localized RCCs. The high ablation rate may be attributable to 3 reasons. 1) The cooled shaft antenna used in this study is capable of generating a large enough ablation zone to encompass the entire tumor. 2) There were relatively strict inclusion criteria, all lesions were less than 4 cm and they were confined by pseudocapsules, which facilitated heat deposition during MW ablation. 3) Real-time peritumor temperature served as an indicator for predicting reliable safety margins. No complications were observed in this study, perhaps in part due to the exclusion of tumors adjacent to the bowel and ureter. Selecting an appropriate puncture route also helped minimize complications. Because MW ablation yielded effective tumor kill in these patients without causing complications, it may become a safe and effective technique for small RCCs at favorable locations. Although this was not a randomized, controlled study of traditional surgical techniques, the low complication rate, minimal side effects, speedy recovery and lower costs strongly favor MW ablation as a curative approach for select small RCCs. This study has some limitations. 1) Inclusion criteria were relatively strict, tumor size was limited to 4 cm or smaller and tumors near the hilum or adjacent to important structures such as the bowel or ureter were excluded. Further studies are needed to include larger RCCs and evaluate the possibility of treating tumors at unfavorable locations. 2) Only 12 patients were included in this study. More patients should be recruited and a prospective, randomized study with surgery should be done to better assess treatment safety and efficacy. 3) Followup is relatively short and we are not certain of the long-term results.
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ULTRASOUND GUIDED PERCUTANEOUS MICROWAVE ABLATION FOR RENAL CANCER
CONCLUSIONS In this pilot study with a short followup ultrasound guided percutaneous MW ablation appeared to be safe and effective for inducing complete necrosis of select small RCCs. Greater experience with this technique should be required before its widespread clinical application.
Abbreviations and Acronyms CT LK MW RCC RF RK
⫽ ⫽ ⫽ ⫽ ⫽ ⫽
computerized tomography left kidney microwave renal cell carcinoma radio frequency right kidney
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17.
18.
19.
20.
21.
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EDITORIAL COMMENT Nephron sparing approaches for renal masses are becoming increasingly used by urologists. Partial nephrectomy (open or laparoscopic) can be performed with low morbidity and it remains the current gold standard treatment for appropriately selected renal masses.1 Other management options for renal masses include active surveillance or minimally invasive therapies that freeze or cook tumors via cryoablation or RF ablation.2 The current study is rather small with 12 patients and it presents pilot data on the feasibility of ultrasound guided percutaneous MW ablation for small renal tumors. It should also be noted that this is a short-term study with a median followup of less than 1 year and the manner in which tumor recurrence was assessed (via CT or ultrasound) may not be entirely accurate. A better understanding of the efficacy of any new technology for treating renal masses may be gained by further evaluation under an ablate and resect type of protocol to determine whether viable tumor is still present after the initial intervention. Furthermore, uncertainty regarding the ablative zone of MW therapy is not well characterized. As our understanding of the natural history of small renal masses continues to evolve, we are beginning to realize that many renal masses that are treated today with surgery may in the future be observed or treated with ablative therapies. Therefore, we must meet the current challenge of properly evaluating the efficacy of new technologies for cancer treatment before we can safely apply these treatments to widespread clinical use. Mark L. Gonzalgo Department of Urology The James Buchanan Brady Urological Institute The Johns Hopkins Hospital Baltimore, Maryland 1.
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Gill IS, Kavoussi LR, Lane BR, Blute ML, Babineau D, Colombo JR et al: Comparison of 1,800 laparoscopic and open partial nephrectomies for single renal tumors. J Urol 2007; 178: 41. Kunkle DA, Egleston BL and Uzzo RG: Excise, ablate or observe: the small renal mass dilemma—a meta-analysis and review. J Urol 2008; 179: 1227.