Cryotherapy is an exciting modality within the energy-based ablation device market, and is set to explode during the next ten years. It is being used primarily in cardiovascular, general surgery, cancer therapy and gynecology, and a good part of its use is thought to be off-label. Cryotherapy was little used in the EU until just recently because of safety laws in place which prohibited the use of the bomb-like pressurized gas tanks required to produce the ultra-cold temperatures. Some companies are working to develop methods of cryotherapy which do not require pressurized gases, so the EU market is likely to eventually increase. In the meantime, the Americas are going strong with cryotherapy.
The global market for cryotherapy will grow at a compound average of almost 20% over the next few years.
Cryotherapy, also called cryosurgery, cryoablation or targeted cryoablation therapy, is a minimally invasive treatment that uses extreme cold to freeze and destroy diseased tissue, including cancer cells. Although cryotherapy and cryoablation can be used interchangeably, the term "cryosurgery" is reserved best for cryotherapy performed using an open, surgical approach. During cryotherapy, liquid nitrogen or argon gas is applied to diseased cells located outside or inside the body. Physicians use image-guidance techniques such as ultrasound, computed tomography (CT) or magnetic resonance (MR) when using cryotherapy inside the body.
Cryotherapy is applied in a freeze-thaw process. The cryotherapy probes, needles or catheters are carefully positioned in place using ultrasound guidance. Once in position, the freezing agent, argon gas, is allowed to circulate through the cryotherapy probes, causing an ice ball to form in the tissue at the tip of the probes. The tissue is frozen rapidly, then thawed slowly and completely, and then is put through a second freeze-thaw cycle. The cooling rate should be as rapid as possible, since faster freezing encourages development of ice crystals within the target tissue cells. This mass of frozen tissue can be viewed during surgery by way of ultrasound. There is no post-operative expansion of killed cells, therefore the cryoablation is limited to the ice ball tissue mass.
Although there is a thermal gradient within the freeze zone, there is a distinct transition between frozen and simply chilled tissue. In the margin tissue, temperatures are a little warmer than at the central zone, and may range from 0° to -20° C. At these temperatures, cell survival is possible. In this region, it is apoptosis and secondary necrosis which cause cell death. Tissue repair begins quickly after the tissue has thawed, and starts with the inflammatory response of lymphocytes and macrophages infiltrating the thawed area. It usually takes a few months for the body to remove the necrotic tissue and replace it with collagen to form a scar. The fact that cryoablation preserves the collagen matrix helps in the tissue repair and healing process.
Ultimately it is the intensity of the freezing that determines the ultimate response of the targeted tissue, which may range from chilled to inflammation to cell death. Minor freezing is accompanied by an inflammatory response. Severe freezing creates intracellular ice which physically disrupts the cell and kills it. However, different cell types show different sensitivities to freezing, a fact which can be used for therapeutic purposes. For example, prostate cancer cells demonstrate different susceptibilities to freezing, which is linked to the presence of the androgen receptor.
Usually, the freezing is applied for approximately 1-3 minutes, then warmer temperatures are allowed to return, usually by flushing the cryo catheter with heated saline, then the process is repeated. The freezing is monitored using temperature sensors both to ensure that target temperatures are achieved (usually, below -40° C, but this depends to an extent on the type of target tissue), and to monitor surrounding tissues in order to protect them from the cold. At the same time, the physician needs to ensure that sufficient margin is frozen so that cancer cells on the edge of the ice ball are ablated as well.
There are challenges in the use of cryoablation. One is achieving total cryoablation when the target tissue has an irregular shape. In such cases, the physician may have to reposition the probes and run through the freeze-thaw cycles again. Another potential problem is skill-related: the physician must be well-trained and sufficiently experienced in the procedure to ensure that the ice ball is large enough and has reached the target temperatures needed for thorough ablation of the diseased tissue. Manufacturers are working to develop devices and procedures to increase ease of use and effectiveness of cryoablation.
Source: MedMarket Diligence, LLC; Report #A145, "Ablation Technologies Worldwide Market, 2009-2019: Products, Technologies, Markets, Companies and Opportunities."