Post-Cryoablation CT Appearances in Renal Cell Carcinoma ... CT Appearances.pdf · detection of...

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Post Post- Cryoablation Cryoablation CT Appearances in Renal CT Appearances in Renal Cell Carcinoma Cell Carcinoma Williams R, Das R, Munneke G, Gonsalves M Introduction Cryoablation refers to any method of destroying tissue by freezing and has been used in the treatment of cancer since the mid 19 th century. Increased use of cross-sectional imaging has resulted in the detection of renal cancers, when smaller and of a lower stage (T1a). The current standard of care for such tumours is partial nephrectomy. Image guided, percutaneous, cryoablation is increasingly recognised as an attractive alternative to surgical techniques because of the low procedural stress response, good safety profile and rapid patient recovery. Mechanism of Action Cell death Cryoablation causes cell death by direct and indirect mechanisms. Intracellular ice-crystal formation leads to damage of organelle and cell membranes. As ablated tissues warm, osmotic fluid shifts lead to cell swelling and bursting. Vessel thrombosis leads to tissue ischaemia and inflammatory cytokine release, producing an unfavourable environment for cell survival. Cell death is directly influenced by four factors: cooling rate, temperature, time at target temperature and thawing rate. Rapid freezing, low temperatures, prolonged time at target temperature and slow thawing all promote cell death. Repeated freeze-thaw cycles will also lead to a greater rate of liquefactive necrosis. Procedure At our institution all cryoablations are performed under general anaesthesia with the patients positioned prone or prone oblique. A post contrast, nephrographic phase, CT is performed through to determine tumour position and relationships to adjacent organs. The number and type of cryoprobes, to be used, are selected and positioned to ensure adequate tumour coverage by the ice-ball. An 18G co-axial needle is sited to facilitate biopsy. (Figure 4) Hydrodissection can be performed to displace adjacent organs from the ablation zone. (Figure 5) Following biopsy, two “freeze-thaw” cycles comprising, 10min freeze, 4min passive thaw, 2min active thaw are performed. Further freeze-thaw cycles can be performed, with needle repositioning if necessary, until an adequate ice ball is achieved. During ablation the skin is protected from frost bite injury by placing damp gauze around the cryoprobes and the gauze repeatedly irrigated. Efficacy and Safety: Technical Success: Initial, technical success rates are high, between 97 4 and 100% 5 . Local tumour progression is reported at between 4.5 - 5.2% . Cancer specific, 5 year survical rates are comparable to those of laparascopic cryoablation at 95% 6,7 Tumours 3cm in size and anterior or central position are associated with worse outcomes. Safety: Haematuria, collecting system leak (figure 6a) and neuropraxia have all been reported but tend to be self-limiting. Major complications occur in approximately 7% of cases and are usually related to haemorrhage (figure 6b) or medical events (Myocardial infarction / CVA). Percutaneous cryoablation appears to result in fewer complications than laparoscopic cryoablation or partial nephrectomy. Length of admission is also shorter, being on average 24hrs. Cooling and Warming: Cryoprobes are inserted into the target tumour. Cooling is achieved by circulating high pressure Argon gas (240ATM) through a narrow opening (throttle) in the tip of the cryoprobe, after which the gas rapidly expands to atmospheric pressure leading to a decrease in the temperature of the gas (Joule-Thompson effect). Warming of tissues is achieved both passively (no gas) and with high pressure helium (150ATM) which warms during expansion. Follow-up Imaging As the treated tumour is left in situ post ablation, follow-up imaging is mandatory to assess outcomes. At our institution this is performed at 3, 6 and 12 months and annually afterwards. Immediate (<4/52) post ablation imaging will show an ablation zone larger than the original tumour, as a margin of parenchyma has been intentionally ablated (Fig 7b). On follow up imaging the ablation zone should be of low attenuation (relative to renal parenchyma) and demonstrate a progressive decrease in size. (Figure 8). In general terms ablated tumours should not enhance, however, 15- 20% may demonstrate a thin rim of peripheral enhancement for several months. Nodular or cresentic enhancement (>10HU) and increasing size of the ablation zone are suggestive of local tumour progression (Figure 9 and 10). Conclusion Percutaneous cryoablation is a safe and effective alternative to nephron sparing surgical techniques in the treatment of T1a renal tumour. Knowledge of the expected intra-procedural and post ablation CT appearances is essential to ensure good outcomes. 1. Clarke D, Robilotto A, Rhee E et al (2007) Cryoablation of renalcancer: variables involved in freezing-induced cell death. TechnolCancer Res Treat 6(2):69–79 2. Williams SK, de la Rosette J, Landman J, Keely FX (2007)Cryoablation of small renal tumors. EAU-EBU Update Series 5:206–218 3.Gage AA, Baust J. Mechanism of tissue injury in cryosurgery. Cryobiology 1998; 37:171-186 4. Atwell TD, Farrell MA , Leibovich BC , et al . Percutaneous renal cryoablation: experience treating 115 tumors . J Urol 2008 ;179 ( 6 ): 2136 – 2140; discussion 2140–2141 5. Rodriguez R, Cizman Z,Georgiades C et al. Prospective Analysis of the Safety and Efficacy of PercutaneousCryoablation for pT1NxMx Biopsy-Proven Renal Cell Carcinoma. Cardiovasc Intervent Radiol (2011) 34:573–578 6. Georgiades CS, Hong K, Bizzell C et al (2008) Safety and efficacyof CT-guided percutaneous cryoablation for renal cellcarcinoma. J Vasc Interv Radiol 19:1302–1310 7. Aron M, Gill IS (2007) Minimally invasive nephron-sparingsurgery (MINSS) for renal tumors. Part II. Probe ablative therapy.Eur Urol 51:348–357 Diagram 2: Cryoprobe and isotherm with demonstration of surrounding temperatures. Diagram 1: Cell death pathway demonstrating intracellular injury, osmotic injury and terminal cell lysis. Figure 3: Cryoprobe with ice-ball Figure 4a: Iceball with viable tumour visible at inferior border Figure 4b: Following further needle placement and freeze-thaw cycle, resulting ice-ball adequately covers tumour Figure 5: Hydrodissection to displace colon from ablation zone Figure 6a Collecting system injury Figure 6b Haemorrhage post cryoablation Figure 7 Pre-treatment CT. Figure 7b 9 days post cryoablation with tumour surrounded by ablated parenchyma. Stranding and haemorrhage within adjacent perinephric fat is shown. Figure 10. Enhancing nodule in the periphery of a tumour, following laparoscopic cryoablation 3 years previously. Findings are in keeping with late recurrence. Recurrent disease was proven at subsequent biopsy and the patient went on to percutaneous cryoablation of the lesion Isotherm: Temperatures of -40ºC are required to ensure tumour kill 2 . Once freezing has commenced the isotherm can be readily visualised on CT imaging as an ice-ball. The temperature is coldest immediately adjacent to the cryoprobe and decreases rapidly with increasing distance. (Diagram 2.) The edge of the visible ice-ball represents a non-lethal temperature of +0.5ºC. The ice ball must extend 5 - 6mm beyond the edge of the target tumour to ensure the tumour is covered by the lethal -40ºC isotherm. Figure 8. Pre-treatment CT (a) Follow-up imaging at 3 (b), 6 (c) and 12 (d) months demonstrating decreasing tumour size. 1758624 Figure 9 a. Pre-treament CT. b. Satisfactory post ablation appearances at 3 months c. Nodular enhancement in the periphery of the ablation zone, at 6 months, indicating Local tumour progression. Biopsy performed at time of ablation showed the tumour to be an oncocytoma and current management plan is for surveillance.

Transcript of Post-Cryoablation CT Appearances in Renal Cell Carcinoma ... CT Appearances.pdf · detection of...

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PostPost--CryoablationCryoablation CT Appearances in Renal CT Appearances in Renal

Cell CarcinomaCell Carcinoma

Williams R, Das R, Munneke G, Gonsalves M

IntroductionCryoablation refers to any method of destroying tissue by freezing and has been used in the treatment of cancer since the mid 19th

century. Increased use of cross-sectional imaging has resulted in the detection of renal cancers, when smaller and of a lower stage (T1a). The current standard of care for such tumours is partial nephrectomy. Image guided, percutaneous, cryoablation is increasingly recognised as an attractive alternative to surgical techniques because of the low procedural stress response, good safety profile and rapid patient recovery.

Mechanism of Action

Cell death

Cryoablation causes cell death by direct and indirect mechanisms. Intracellular ice-crystal formation leads to damage of organelle and cell membranes. As ablated tissues warm, osmotic fluid shifts lead to cell swelling and bursting. Vessel thrombosis leads to tissue ischaemia and inflammatory cytokine release, producing an unfavourable environment for cell survival.

Cell death is directly influenced by four factors: cooling rate,temperature, time at target temperature and thawing rate. Rapid freezing, low temperatures, prolonged time at target temperature and slow thawing all promote cell death. Repeated freeze-thaw cycles will also lead to a greater rate of liquefactive necrosis.

ProcedureAt our institution all cryoablations are performed under general anaesthesia with the patients positioned prone or prone oblique.

A post contrast, nephrographic phase, CT is performed through to determine tumour position and relationships to adjacent organs. The number and type of cryoprobes, to be used, are selected and positioned to ensure adequate tumour coverage by the ice-ball. An 18G co-axial needle is sited to facilitate biopsy. (Figure 4)

Hydrodissection can be performed to displace adjacent organs from the ablation zone. (Figure 5) Following biopsy, two “freeze-thaw”cycles comprising, 10min freeze, 4min passive thaw, 2min active thaw are performed. Further freeze-thaw cycles can be performed, with needle repositioning if necessary, until an adequate ice ball isachieved. During ablation the skin is protected from frost bite injury by placing damp gauze around the cryoprobes and the gauze repeatedly irrigated.

Efficacy and Safety:

Technical Success:

Initial, technical success rates are high, between 974 and 100%5. Local tumour progression is reported at between 4.5 - 5.2% . Cancer specific, 5 year survical rates are comparable to those of laparascopiccryoablation at ≥95%6,7 Tumours ≥ 3cm in size and anterior or central position are associated with worse outcomes.

Safety:

Haematuria, collecting system leak (figure 6a) and neuropraxia have all been reported but tend to be self-limiting. Major complications occur in approximately 7% of cases and are usually related to haemorrhage (figure 6b) or medical events (Myocardial infarction / CVA). Percutaneous cryoablation appears to result in fewer complications than laparoscopic cryoablation or partial nephrectomy. Length of admission is also shorter, being on average 24hrs.

Cooling and Warming:

Cryoprobes are inserted into the target tumour. Cooling is achieved by circulating high pressure Argon gas (≥240ATM) through a narrow opening (throttle) in the tip of the cryoprobe, after which the gas rapidly expands to atmospheric pressure leading to a decrease in the temperature of the gas (Joule-Thompson effect). Warming of tissues is achieved both passively (no gas) and with high pressure helium (≥150ATM) which warms during expansion.

Follow-up ImagingAs the treated tumour is left in situ post ablation, follow-up imaging is mandatory to assess outcomes. At our institution this is performed at 3, 6 and 12 months and annually afterwards. Immediate (<4/52) post ablation imaging will show an ablation zone larger than the original tumour, as a margin of parenchyma has been intentionally ablated (Fig 7b). On follow up imaging the ablation zone should be of low attenuation (relative to renal parenchyma) and demonstrate a progressive decrease in size. (Figure 8).

In general terms ablated tumours should not enhance, however, 15-20% may demonstrate a thin rim of peripheral enhancement for several months. Nodular or cresentic enhancement (>10HU) and increasing size of the ablation zone are suggestive of local tumour progression (Figure 9 and 10).

ConclusionPercutaneous cryoablation is a safe and effective alternative to nephron sparing surgical techniques in the treatment of T1a renal tumour. Knowledge of the expected intra-procedural and post ablation CT appearances is essential to ensure good outcomes.

1. Clarke D, Robilotto A, Rhee E et al (2007) Cryoablation of renalcancer: variables involved in freezing-induced cell death. TechnolCancer Res Treat 6(2):69–792. Williams SK, de la Rosette J, Landman J, Keely FX (2007)Cryoablation of small renal tumors. EAU-EBU Update Series 5:206–2183.Gage AA, Baust J. Mechanism of tissue injury in cryosurgery. Cryobiology 1998; 37:171-186 4. Atwell TD, Farrell MA , Leibovich BC , et al . Percutaneous renal cryoablation: experience treating 115 tumors . J Urol 2008 ;179 ( 6 ): 2136 – 2140; discussion 2140–21415. Rodriguez R, Cizman Z,Georgiades C et al. Prospective Analysis of the Safety and Efficacy of PercutaneousCryoablation for pT1NxMx Biopsy-Proven Renal Cell Carcinoma. Cardiovasc Intervent Radiol(2011) 34:573–5786. Georgiades CS, Hong K, Bizzell C et al (2008) Safety and efficacyof CT-guided percutaneous cryoablation for renal cellcarcinoma. J Vasc Interv Radiol 19:1302–13107. Aron M, Gill IS (2007) Minimally invasive nephron-sparingsurgery (MINSS) for renal tumors. Part II. Probe ablative therapy.Eur Urol 51:348–357

Diagram 2: Cryoprobe and isotherm with demonstration of surrounding temperatures.

Diagram 1: Cell death pathway demonstrating intracellular injury, osmotic injury and terminal cell lysis.

Figure 3: Cryoprobe with ice-ball

Figure 4a: Iceball with viable tumour visible at inferior border

Figure 4b: Following further needle placement and freeze-thaw cycle, resulting ice-ball adequately covers tumour

Figure 5: Hydrodissection to displace colon from ablation zone

Figure 6a Collecting system injury Figure 6b Haemorrhage post cryoablation

Figure 7 Pre-treatment CT. Figure 7b 9 days post cryoablation with tumour surrounded by ablated parenchyma. Stranding and haemorrhage within adjacent perinephric fat is shown.

Figure 10. Enhancing nodule in the periphery of a tumour, following laparoscopic cryoablation 3 years previously. Findings are in keeping with late recurrence. Recurrent disease was proven at subsequent biopsy and the patient went on to percutaneous cryoablation of the lesion

Isotherm:

Temperatures of -40ºC are required to ensure tumour kill2. Once freezing has commenced the isotherm can be readily visualised on CT imaging as an ice-ball. The temperature is coldest immediately adjacent to the cryoprobe and decreases rapidly with increasing distance. (Diagram 2.) The edge of the visible ice-ball represents a non-lethal temperature of +0.5ºC. The ice ball must extend 5 - 6mm beyond the edge of the target tumour to ensure the tumour is covered by the lethal -40ºC isotherm.

Figure 8. Pre-treatment CT (a) Follow-up imaging at 3 (b), 6 (c) and 12 (d) months demonstrating decreasing tumour size.

1758624

Figure 9 a. Pre-treament CT. b. Satisfactory post ablation appearances at 3 months c. Nodular enhancement in the periphery of the ablation zone, at 6 months, indicating Local tumour progression. Biopsy performed at time of ablation showed the tumour to be an oncocytoma and current management plan is for surveillance.