Cryoablation

Cryoablation refers to the use of thermal energy in the form of very low temperatures to achieve targeted destruction of tumor cells. It is an image-guided technique, currently widely employed in the management of renal ¹, hepatic ² and lung tumors ³.

Historically, a rudimental form of cryosurgery was employed in the 1800s, when iced saline solutions were used to treat locally advanced breast and cervical cancers, as well as dermatological malignancies ⁴. Its role has now been extended to the treatment of internal organ neoplasias. The evidence behind the capacity of cryoablation to destroy tumor tissue is overwhelming ^5,6.

Mechanism of action

During cryoablation, one or more specifically designed needles (cryoprobes) are placed under direct imaging in the desired area. Tumor destruction is thought to be achieved via different mechanisms:

1. mechanical: closer to the cryoprobe, the lowest (up to -40 degrees Celsius) temperatures are achieved. A sudden temperature drop translates into intracellular ice formation, damaging intracellular organelles and the cell wall ⁴.

2. osmotic: more peripherally, relatively higher temperatures (-20 to 0 degrees Celsius) might be unable to create intracellular ice but can form ice crystals in the extracellular compartment. In the following thawing cycle, the newly liquified, electrolyte-rich interstitial fluid can passively diffuse into the cells suddenly altering their concentration of solutes and key metabolic processes ⁴. For this reason, the thawing cycle is an absolutely crucial part of the cryoablation procedure.

3. ischemic: local hypothermia is expected to have an effect on blood and oxygen supply, exacerbating the tissue damage during the ablation process⁷.

4. immunologic: animal studies have suggested a possible sensitization of the immune system, that would then target and destroy residual sublethally injured tumor tissue ⁸. This theory however is currently disputed and not widely accepted.

Multiple parameters influence the outcome of tumor cell destruction, among which are the end-temperature, the length of the freezing cycle, and the thawing temperature and its rate. Due to tissue and vascular inhomogeneities, the effect of cryoablation on tissues is hard to confidently predict in vivo ⁴.

Cryoprobe design

The key element of the cryoprobe is an expansion chamber, located at the end of the needle. Exploiting the Joule-Thompson effect (i.e. compression or expansion of gases results in a change in their temperature), a cryogenic gas (usually argon) is allowed to expand at the tip of the needle, thus lowering its temperature. The opposite occurs in the thawing phase, where argon is replaced by another agent (e.g. helium) with opposite properties (e.g. helium, which increases in temperature during expansion).

The desired reversal of temperature in the thawing process can also be achieved by heating the cryoprobe using an electrical current, depending on machine set-up.

Imaging

The shape and size of the ablation zone depend on the tissue characteristics, as well as the number and properties of the cryoprobes. On ultrasonography, it is seen as a hyperechoic line with posterior acoustic shadowing, mirroring the surface of the ice ball; on CT, it is a well defined water density low-attenuation region. Its hallmark on MRI is a flow-void region ⁹.

Procedure

1. under sterile conditions, verify that there is no gaz leak from the cryoprobes by inserting them in water

2. make sure that cooling and active heating are functional

3. US or CT-guided insertion of cryoprobes in the lesion - the number of cryoprobes and location depend on the size of the lesion

Freeze–thaw cycles

_{They are variable, depending on location of the lesion, institutions and operators.}

• lung triple-freeze protocol

  • freezing for 3 min, then 2 min of passive heating, 1 min of active heating, 7 min of freezing - after this cycle a CT control may be performed

  • passive heating for 6 min, active heating for 1 min, freezing for 10 min

  • active heating and removal of cryoprobes

Advantages

• unlike in radiofrequency (RFA) or microwave ablation (MWA) interventions, the ice ball that is created during cryoablation is observable in real time. This means that if the ablation zone is found to be suboptimal, additional probes can be placed or the freezing cycle can be prolonged. Also, inadvertent involvement of non-target structures can be detected early during the procedure, thus avoiding or minimizing complications.

• cryoablation can potentially be undertaken under local anesthesia and conscious sedation (although it is more often performed under general anesthesia)

• it is reported to be less painful in the post-intervention period compared to other ablation techniques ³

Disadvantages

• the ablation zone achievable with cryoablation is smaller than the one created with RFA or MWA; this means that more probes are required, increasing the complication rates

• cryoablation is more time-consuming; in addition to the need for multiple probes, a typical procedure would require two freezing cycles with a thawing phase in between (versus, for example, a single 2-minute cycle during an MWA procedure)

• like RFA and MWA, cryoablation can also result in post-ablation syndrome, a flu-like illness due to systemic response: very rarely, this can assume severe proportions encompassing coagulopathy and multiorgan failure, defined as cryoshock ¹⁰