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Treatment of a Juxtaglomerular Tumour with Radiofrequency Ablation
Case Report Treatment of a Juxtaglomerular Tumour with Radiofrequency Ablation Alexander P. S. Kirkham, Stephen G. F. Ho, Ryan F. Paterson, Michelle D. Johnson, and Silvia D. Chang Juxtaglomerular tumors, or reninomas, are a rare cause of hypertension, almost always benign and accurately localized by a combination of biochemical tests and imaging. Because the tumors are usually small at presentation, and there are good markers for recurrence, we consider treatment by radiofrequency ablation a useful alternative to nephron-sparing surgery and describe its use in one patient. UROLOGY 71: 168.e1–168.e4, 2008. © 2008 Elsevier Inc.
T
umors of the juxtaglomerular apparatus of the kidney, sometimes also called reninomas, are a rare cause of hypertension. First described in 1967, they almost never metastasise.1 Only one case report has been reported of a large tumor spreading to the lungs 6 years after nephrectomy.2 Presentation in the largest series so far published was in patients between 13 and 53 years old, with severe, symptomatic hypertension, and a mean tumor diameter of 2.4 cm.1 Because the tumor is small, often occurs in young patients, and is in almost all cases benign, the current optimal treatment has moved from nephrectomy to nephron-sparing surgery, either open3 or laparoscopic.4 Such an approach depends on imaging to localize the tumor, which is in most cases visible on computed tomography (CT)5 or magnetic resonance imaging (MRI).6 Radiofrequency ablation (RFA) has recently been used to treat small renal cell carcinomas.7 Given that there are both clinical (hypertension) and biochemical (elevated renin levels) markers for recurrence, and the benign nature of the tumor, we consider radiofrequency ablation a useful alternative to surgery and describe its use in one patient.
CASE REPORT A 17-year-old woman presented with a history of polyuria and polydipsia, headaches, and blurred vision. In the emergency room her blood pressure was 210/110 mmHg; her serum sodium was normal but the potassium was 1.7 mmol/L. Initial treatment was with antihypertensive medications: labetalol and diltiazem, rendering her normotensive, and with potassium chloride elixir. While the pa-
From the Departments of Radiology and Urology, Vancouver General Hospital; and the Department of Endocrinology, St Paul’s Hospital, Vancouver, British Columbia, Canada Reprint requests: Dr. Alex Kirkham, 61, Warneford Street, London E9 7NG, United Kingdom. E-mail: [email protected] Submitted: April 26, 2007, accepted (with revisions): September 20, 2007
© 2008 Elsevier Inc. All Rights Reserved
tient received antihypertensives (but not an angiotensin converting enzyme inhibitor), her blood electrolytes were normal but the serum aldosterone was at the upper limit of normal: 383 pmol/L (normal range, 30 to 415), and supine plasma renin activity was markedly raised at 4.8 ng/L/s (normal, less than 0.28). An unenhanced CT of the abdomen showed normal adrenals but a 7-mm-diameter hyperdense area in the upper pole of the right kidney. An MRI 1 week later also showed an 8-mm area in same location, slightly hypointense on T2-weighted sequences and enhancing poorly in the arterial phase. Ultrasound showed an echopoor lesion in the right upper pole. Because we believed the clinical findings were likely the result of either renal vascular disease or a reninoma, we performed a CT angiogram and bilateral renal vein sampling. The CT was normal but for the previously imaged right upper pole lesion, which was slightly hypodense in the arterial phase after contrast. The vein sampling showed renin activity of 3.96 and 4.40 ng/L/s in the right and left renal veins, respectively: it did not help to lateralize the tumor. A follow-up MR scan 10 months later (Fig. 1) showed an unchanged lesion in the right kidney. Although the patient’s blood pressure and symptoms were well controlled on antihypertensives, the plasma renin activity remained high and she elected to undergo definitive treatment. The surgical options (laparoscopic and open partial nephrectomy) were discussed, together with radiofrequency ablation. She opted for the latter. We performed RFA using general anesthetic. With the patient semiprone in the CT suite, we identified the lesion with both ultrasound and enhanced CT (Fig. 2). A 15-gauge sheath was placed with its tip abutting the superficial aspect of the lesion in the upper pole of the right kidney, and through it we obtained two 18-gauge cm core biopsies. Given the high probability of a juxtaglomerular tumor, we did not request frozen sections, but the unexpected finding of a renal cell carcinoma after 0090-4295/08/$34.00 168.e1 doi:10.1016/j.urology.2007.09.039
Figure 1. Pretreatment MR images of the mass in the right kidney. In each case the white arrow indicates tumor (GE Twinspeed 1.5T magnet). (a) T2-weighted fast spin echo fat-saturated axial image (TE 104 milliseconds, TR 1.1 seconds, echo train length 17, matrix 256 ⫻ 224, slice width 8 mm). (b) Single shot fast spin echo sagittal image (TE 98 milliseconds, TR 981 milliseconds, matrix 256 ⫻ 192, slice width 6 mm). (c) Dynamic postgadolinium gradient echo axial image: arterial phase (TE 4.2 milliseconds, TR 150 milliseconds, flip angle 70°, matrix 256 ⫻ 160, slice width 8 mm. Contrast: 20 mL gadiodiamide (0.2 mmol/kg) at 2 mL/s: arterial image acquisition at 20 seconds, venous at 60 seconds). (d) Dynamic postgadolinium gradient echo axial image: venous phase. Note that the lesion is much less conspicuous than in the arterial phase.
ablation would have prompted close follow-up and possibly surgical resection. We then placed a Boston Scientific (Natick, MA) Le Veen probe with 3.5-cm treatment wires in the lesion, with the wires deployed to 80% of their maximum diameter (Fig. 2). A protective pneumoretroperitoneum was produced by injecting 50 mL of CO2 through a 22-gauge spinal needle, separating the kidney from the liver. We then followed a standard ablation protocol with two 168.e2
treatment phases. In the first, total treatment time was 11 minutes 11 seconds, with a maximum power of 180 W. In the second, treatment was for 3 minutes 11 seconds, with a maximum power of 126 W.
RESULTS The core biopsies of the lesion confirmed a juxtaglomerular tumor. The immediate post-treatment conUROLOGY 71 (1), 2008
Figure 2. Contrast-enhanced CT images of the right kidney at RFA (GE HiSpeed single detector spiral scanner, 5-mm slices). (a) Cortical phase just before treatment (35-second delay after 120 mL intravenous ioversol 320 at 3 mL/s). (b,c) Image after placement of a 3.5-cm Boston Scientific LeVeen probe. Note the concentric antennae fanning out from the hollow sheath. The second image (c) is after formation of a protective air cavity in the retroperitoneum (white arrow) with a further small needle. (d,e) Defects in the kidney (white arrow) and liver (black arrow) after treatment.
UROLOGY 71 (1), 2008
168.e3
trast-enhanced CT (Fig. 2) showed a nonenhancing ablation zone enveloping the site of the lesion, and a small (lesss than 2 cm) area of hypodensity in the adjacent liver. Post-treatment blood pressure was normal without antihypertensives, and blood pressure, serum potassium, renin, creatanine and aldosterone have remained normal for 14 months. A follow-up MR of the kidneys performed 2 months after treatment confirmed the ablation zone and a small area of altered signal within the liver.
COMMENT Although general elevation of plasma renin activity is a constant finding in patients with symptomatic juxtaglomerular tumors, it is not specific and may more commonly occur in renal artery stenosis or renal parenchymal disease. Once these causes have been excluded, the tumor needs to be localized before treatment. Selective sampling of the renal veins (the original method) enables reliable determination of side in only 64% of patients1 and the ultrasound findings are variable: the lesion may be hyper or hyoechoic.1 CT and MR are probably more sensitive, with the key finding being reduced enhancement after intravenous contrast compared with surrounding renal parenchyma.6,8 In the largest series so far published, with eight patients,1 CT showed the tumor in each, but neither the CT nor the MR signs are specific1,5,6 and small renal cell carcinomas are impossible to exclude. Work in three patients has, however, suggested a difference in enhancement pattern, with juxtaglomerular tumors enhancing poorly at 1 minute and moderately at 5 minutes, in contrast to the early enhancement seen with renal cell carcinomas.8 In the kidney, RFA has been studied in several series (many with mean follow-up under 2 years9) and most authors now report complete ablation in well over 90%.7,9 The tumor diameter is ideally 4 cm or less, although masses up to 5.5 cm have been ablated successfully.7 Large tumors require overlapping treatment volumes or multiple electrodes, and sometimes follow-up treatments.7 The major complication rate is very low (around 2%),9 but pain at the skin entry site, hematoma, urinoma, ureteric stricture, and injury to surrounding structures, in particular the large bowel, have been reported.10 A recent study in a small number of patients confirms that although it depends on the size of the lesion, the impairment in renal function (measured by clearance of MAG3) is limited with RFA.11 Impairment in function is significant with partial nephrectomy, even in children,12 and urine leak, hematoma, and acute renal failure are recognized complications.13 A comparison between RFA and nephron-sparing surgery has not yet been performed,
168.e4
long-term results from the former are not yet available,9 but there is some evidence that local tumor control is better with nephron-sparing surgery than with current ablative techniques.14 Residual tumor has been found after some apparently successful ablations at subsequent nephrectomy.15 However, a small chance of local recurrence may well be acceptable for an almost always benign tumor for which there are good clinical and biochemical markers. A further possibility in our patient would have been cryoablation, and there is debate about whether it is superior to RFA; both have their advocates.7,14 In conclusion, small reninoma that can be targeted accurately may be suitable for RFA, which is less invasive than nephron-sparing surgery and results in excellent preservation of renal function.
References 1. Haab F, Duclos JM, Guyenne T, et al: Renin secreting tumors: diagnosis, conservative surgical approach and long-term results. J Urol 153: 1781–1784, 1995. 2. Duan X, Bruneval P, Hammadeh R, et al: Metastatic juxtaglomerular cell tumor in a 52-year-old man. Am J Surg Pathol 28: 1098 –1102, 2004. 3. Mete UK, Niranjan J, Kusum J, et al: Reninoma treated with nephron-sparing surgery. Urology 61: 1259, 2003. 4. Feliciotti F, Campagnacci R, Perretta S, et al: Laparoscopic resection of a juxtaglomerular cell tumor of the right kidney. Surg Endosc 16: 539, 2002. 5. Rubenstein JN, Eggener SE, Pins MR, et al: Juxtaglomerular apparatus tumor: a rare, surgically correctable cause of hypertension. Rev Urol 4: 192–195, 2002. 6. Agrawal R, Jafri SZ, Gibson DP, et al: Juxtaglomerular cell tumor: MR findings. J Comput Assist Tomogr 19: 140 –142, 1995. 7. Schiller JD, Gervais DA, and Mueller PR: Radiofrequency ablation of renal cell carcinoma. Abdom Imaging 30: 442– 450, 2005. 8. Tanabe A, Naruse M, Ogawa T, et al: Dynamic computer tomography is useful in the differential diagnosis of juxtaglomerular cell tumor and renal cell carcinoma. Hypertens Res 24: 331–336, 2001. 9. Aron M, and Gill IS: Minimally invasive nephron-sparing surgery (MINSS) for renal tumours. Eur Urol 51: 348 –357, 2007. 10. Weizer AZ, Raj GV, O’Connell M, et al: Complications after percutaneous radiofrequency ablation of renal tumors. Urology 66: 1176 –1180, 2005. 11. Mukai T, Sato S, Iguchi T, et al: Effects of radiofrequency ablation on individual renal function: assessment by technetium-99m mercaptoacetyltriglycine renal scintigraphy. Acta Med Okayama 60: 85–91, 2006. 12. Cozzi F, Schiavetti A, Morini F, et al: Renal function adaptation in children with unilateral renal tumors treated with nephron sparing surgery or nephrectomy. J Urol 174: 1404 –1408, 2005. 13. Saranchuk JW, Touijer AK, Hakimian P, et al: Partial nephrectomy for patients with a solitary kidney: the Memorial Sloan-Kettering experience. BJU Int 94: 1323–1328, 2004. 14. Weld KJ, and Landman J: Comparison of cryoablation, radiofrequency ablation and high-intensity focused ultrasound for treating small renal tumours. BJU Int 96: 1224 –1229, 2005. 15. Rendon RA, Kachura JR, Sweet JM, et al: The uncertainty of radio frequency treatment of renal cell carcinoma: findings at immediate and delayed nephrectomy. J Urol 167: 1587–1592, 2002.
UROLOGY 71 (1), 2008
T
umors of the juxtaglomerular apparatus of the kidney, sometimes also called reninomas, are a rare cause of hypertension. First described in 1967, they almost never metastasise.1 Only one case report has been reported of a large tumor spreading to the lungs 6 years after nephrectomy.2 Presentation in the largest series so far published was in patients between 13 and 53 years old, with severe, symptomatic hypertension, and a mean tumor diameter of 2.4 cm.1 Because the tumor is small, often occurs in young patients, and is in almost all cases benign, the current optimal treatment has moved from nephrectomy to nephron-sparing surgery, either open3 or laparoscopic.4 Such an approach depends on imaging to localize the tumor, which is in most cases visible on computed tomography (CT)5 or magnetic resonance imaging (MRI).6 Radiofrequency ablation (RFA) has recently been used to treat small renal cell carcinomas.7 Given that there are both clinical (hypertension) and biochemical (elevated renin levels) markers for recurrence, and the benign nature of the tumor, we consider radiofrequency ablation a useful alternative to surgery and describe its use in one patient.
CASE REPORT A 17-year-old woman presented with a history of polyuria and polydipsia, headaches, and blurred vision. In the emergency room her blood pressure was 210/110 mmHg; her serum sodium was normal but the potassium was 1.7 mmol/L. Initial treatment was with antihypertensive medications: labetalol and diltiazem, rendering her normotensive, and with potassium chloride elixir. While the pa-
From the Departments of Radiology and Urology, Vancouver General Hospital; and the Department of Endocrinology, St Paul’s Hospital, Vancouver, British Columbia, Canada Reprint requests: Dr. Alex Kirkham, 61, Warneford Street, London E9 7NG, United Kingdom. E-mail: [email protected] Submitted: April 26, 2007, accepted (with revisions): September 20, 2007
© 2008 Elsevier Inc. All Rights Reserved
tient received antihypertensives (but not an angiotensin converting enzyme inhibitor), her blood electrolytes were normal but the serum aldosterone was at the upper limit of normal: 383 pmol/L (normal range, 30 to 415), and supine plasma renin activity was markedly raised at 4.8 ng/L/s (normal, less than 0.28). An unenhanced CT of the abdomen showed normal adrenals but a 7-mm-diameter hyperdense area in the upper pole of the right kidney. An MRI 1 week later also showed an 8-mm area in same location, slightly hypointense on T2-weighted sequences and enhancing poorly in the arterial phase. Ultrasound showed an echopoor lesion in the right upper pole. Because we believed the clinical findings were likely the result of either renal vascular disease or a reninoma, we performed a CT angiogram and bilateral renal vein sampling. The CT was normal but for the previously imaged right upper pole lesion, which was slightly hypodense in the arterial phase after contrast. The vein sampling showed renin activity of 3.96 and 4.40 ng/L/s in the right and left renal veins, respectively: it did not help to lateralize the tumor. A follow-up MR scan 10 months later (Fig. 1) showed an unchanged lesion in the right kidney. Although the patient’s blood pressure and symptoms were well controlled on antihypertensives, the plasma renin activity remained high and she elected to undergo definitive treatment. The surgical options (laparoscopic and open partial nephrectomy) were discussed, together with radiofrequency ablation. She opted for the latter. We performed RFA using general anesthetic. With the patient semiprone in the CT suite, we identified the lesion with both ultrasound and enhanced CT (Fig. 2). A 15-gauge sheath was placed with its tip abutting the superficial aspect of the lesion in the upper pole of the right kidney, and through it we obtained two 18-gauge cm core biopsies. Given the high probability of a juxtaglomerular tumor, we did not request frozen sections, but the unexpected finding of a renal cell carcinoma after 0090-4295/08/$34.00 168.e1 doi:10.1016/j.urology.2007.09.039
Figure 1. Pretreatment MR images of the mass in the right kidney. In each case the white arrow indicates tumor (GE Twinspeed 1.5T magnet). (a) T2-weighted fast spin echo fat-saturated axial image (TE 104 milliseconds, TR 1.1 seconds, echo train length 17, matrix 256 ⫻ 224, slice width 8 mm). (b) Single shot fast spin echo sagittal image (TE 98 milliseconds, TR 981 milliseconds, matrix 256 ⫻ 192, slice width 6 mm). (c) Dynamic postgadolinium gradient echo axial image: arterial phase (TE 4.2 milliseconds, TR 150 milliseconds, flip angle 70°, matrix 256 ⫻ 160, slice width 8 mm. Contrast: 20 mL gadiodiamide (0.2 mmol/kg) at 2 mL/s: arterial image acquisition at 20 seconds, venous at 60 seconds). (d) Dynamic postgadolinium gradient echo axial image: venous phase. Note that the lesion is much less conspicuous than in the arterial phase.
ablation would have prompted close follow-up and possibly surgical resection. We then placed a Boston Scientific (Natick, MA) Le Veen probe with 3.5-cm treatment wires in the lesion, with the wires deployed to 80% of their maximum diameter (Fig. 2). A protective pneumoretroperitoneum was produced by injecting 50 mL of CO2 through a 22-gauge spinal needle, separating the kidney from the liver. We then followed a standard ablation protocol with two 168.e2
treatment phases. In the first, total treatment time was 11 minutes 11 seconds, with a maximum power of 180 W. In the second, treatment was for 3 minutes 11 seconds, with a maximum power of 126 W.
RESULTS The core biopsies of the lesion confirmed a juxtaglomerular tumor. The immediate post-treatment conUROLOGY 71 (1), 2008
Figure 2. Contrast-enhanced CT images of the right kidney at RFA (GE HiSpeed single detector spiral scanner, 5-mm slices). (a) Cortical phase just before treatment (35-second delay after 120 mL intravenous ioversol 320 at 3 mL/s). (b,c) Image after placement of a 3.5-cm Boston Scientific LeVeen probe. Note the concentric antennae fanning out from the hollow sheath. The second image (c) is after formation of a protective air cavity in the retroperitoneum (white arrow) with a further small needle. (d,e) Defects in the kidney (white arrow) and liver (black arrow) after treatment.
UROLOGY 71 (1), 2008
168.e3
trast-enhanced CT (Fig. 2) showed a nonenhancing ablation zone enveloping the site of the lesion, and a small (lesss than 2 cm) area of hypodensity in the adjacent liver. Post-treatment blood pressure was normal without antihypertensives, and blood pressure, serum potassium, renin, creatanine and aldosterone have remained normal for 14 months. A follow-up MR of the kidneys performed 2 months after treatment confirmed the ablation zone and a small area of altered signal within the liver.
COMMENT Although general elevation of plasma renin activity is a constant finding in patients with symptomatic juxtaglomerular tumors, it is not specific and may more commonly occur in renal artery stenosis or renal parenchymal disease. Once these causes have been excluded, the tumor needs to be localized before treatment. Selective sampling of the renal veins (the original method) enables reliable determination of side in only 64% of patients1 and the ultrasound findings are variable: the lesion may be hyper or hyoechoic.1 CT and MR are probably more sensitive, with the key finding being reduced enhancement after intravenous contrast compared with surrounding renal parenchyma.6,8 In the largest series so far published, with eight patients,1 CT showed the tumor in each, but neither the CT nor the MR signs are specific1,5,6 and small renal cell carcinomas are impossible to exclude. Work in three patients has, however, suggested a difference in enhancement pattern, with juxtaglomerular tumors enhancing poorly at 1 minute and moderately at 5 minutes, in contrast to the early enhancement seen with renal cell carcinomas.8 In the kidney, RFA has been studied in several series (many with mean follow-up under 2 years9) and most authors now report complete ablation in well over 90%.7,9 The tumor diameter is ideally 4 cm or less, although masses up to 5.5 cm have been ablated successfully.7 Large tumors require overlapping treatment volumes or multiple electrodes, and sometimes follow-up treatments.7 The major complication rate is very low (around 2%),9 but pain at the skin entry site, hematoma, urinoma, ureteric stricture, and injury to surrounding structures, in particular the large bowel, have been reported.10 A recent study in a small number of patients confirms that although it depends on the size of the lesion, the impairment in renal function (measured by clearance of MAG3) is limited with RFA.11 Impairment in function is significant with partial nephrectomy, even in children,12 and urine leak, hematoma, and acute renal failure are recognized complications.13 A comparison between RFA and nephron-sparing surgery has not yet been performed,
168.e4
long-term results from the former are not yet available,9 but there is some evidence that local tumor control is better with nephron-sparing surgery than with current ablative techniques.14 Residual tumor has been found after some apparently successful ablations at subsequent nephrectomy.15 However, a small chance of local recurrence may well be acceptable for an almost always benign tumor for which there are good clinical and biochemical markers. A further possibility in our patient would have been cryoablation, and there is debate about whether it is superior to RFA; both have their advocates.7,14 In conclusion, small reninoma that can be targeted accurately may be suitable for RFA, which is less invasive than nephron-sparing surgery and results in excellent preservation of renal function.
References 1. Haab F, Duclos JM, Guyenne T, et al: Renin secreting tumors: diagnosis, conservative surgical approach and long-term results. J Urol 153: 1781–1784, 1995. 2. Duan X, Bruneval P, Hammadeh R, et al: Metastatic juxtaglomerular cell tumor in a 52-year-old man. Am J Surg Pathol 28: 1098 –1102, 2004. 3. Mete UK, Niranjan J, Kusum J, et al: Reninoma treated with nephron-sparing surgery. Urology 61: 1259, 2003. 4. Feliciotti F, Campagnacci R, Perretta S, et al: Laparoscopic resection of a juxtaglomerular cell tumor of the right kidney. Surg Endosc 16: 539, 2002. 5. Rubenstein JN, Eggener SE, Pins MR, et al: Juxtaglomerular apparatus tumor: a rare, surgically correctable cause of hypertension. Rev Urol 4: 192–195, 2002. 6. Agrawal R, Jafri SZ, Gibson DP, et al: Juxtaglomerular cell tumor: MR findings. J Comput Assist Tomogr 19: 140 –142, 1995. 7. Schiller JD, Gervais DA, and Mueller PR: Radiofrequency ablation of renal cell carcinoma. Abdom Imaging 30: 442– 450, 2005. 8. Tanabe A, Naruse M, Ogawa T, et al: Dynamic computer tomography is useful in the differential diagnosis of juxtaglomerular cell tumor and renal cell carcinoma. Hypertens Res 24: 331–336, 2001. 9. Aron M, and Gill IS: Minimally invasive nephron-sparing surgery (MINSS) for renal tumours. Eur Urol 51: 348 –357, 2007. 10. Weizer AZ, Raj GV, O’Connell M, et al: Complications after percutaneous radiofrequency ablation of renal tumors. Urology 66: 1176 –1180, 2005. 11. Mukai T, Sato S, Iguchi T, et al: Effects of radiofrequency ablation on individual renal function: assessment by technetium-99m mercaptoacetyltriglycine renal scintigraphy. Acta Med Okayama 60: 85–91, 2006. 12. Cozzi F, Schiavetti A, Morini F, et al: Renal function adaptation in children with unilateral renal tumors treated with nephron sparing surgery or nephrectomy. J Urol 174: 1404 –1408, 2005. 13. Saranchuk JW, Touijer AK, Hakimian P, et al: Partial nephrectomy for patients with a solitary kidney: the Memorial Sloan-Kettering experience. BJU Int 94: 1323–1328, 2004. 14. Weld KJ, and Landman J: Comparison of cryoablation, radiofrequency ablation and high-intensity focused ultrasound for treating small renal tumours. BJU Int 96: 1224 –1229, 2005. 15. Rendon RA, Kachura JR, Sweet JM, et al: The uncertainty of radio frequency treatment of renal cell carcinoma: findings at immediate and delayed nephrectomy. J Urol 167: 1587–1592, 2002.
UROLOGY 71 (1), 2008